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Randhi R, Damon M, Dixon KJ. Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice. BMC Gastroenterol 2021; 21:243. [PMID: 34049483 PMCID: PMC8161932 DOI: 10.1186/s12876-021-01827-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/19/2021] [Indexed: 11/12/2022] Open
Abstract
Background Symptoms associated with acute pancreatitis can be debilitating, and treatment remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of acute pancreatitis. Methods Acute pancreatitis was induced in adult male C57Bl/6J mice by administering cerulein (8 injections of 50 µg/kg I.P., spaced an hour apart), with XPro1595 (10 mg/kg, S.C.) or vehicle being administered approximately 18 h after the last injection. Serum was collected 6 or 18 h after the last cerulein injection, pancreatic tissue was collected 2 and 7 days post-induction, and brain hippocampal tissue was collected at 7 days post-induction. The animal’s pain level was assessed 3, 5 and 7 days post-induction. Results The induction of acute pancreatitis promoted a strong increase in serum amylase levels, which had receded back to baseline levels by the next morning. XPro1595 treatment began after amylase levels had subsided at 18 h, and prevented pancreatic immune cell infiltration, that subsequently prevented tissue disruption and acinar cell death. These improvements in pathology were associated with a significant reduction in mechanical hypersensitivity (neuropathic pain). XPro1595 treatment also prevented an increase in hippocampal astrocyte reactivity, that may be associated with the prevention of neuropathic pain in this mouse model. Conclusion Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of cerulein-induced pancreatitis in mice, which provides support of its use in patients with pancreatitis.
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Affiliation(s)
- Rajasa Randhi
- Department of Surgery, Virginia Commonwealth University, 1101 E. Marshall St, Richmond, VA, 23298, USA
| | - Melissa Damon
- Department of Surgery, Virginia Commonwealth University, 1101 E. Marshall St, Richmond, VA, 23298, USA
| | - Kirsty J Dixon
- Department of Surgery, Virginia Commonwealth University, 1101 E. Marshall St, Richmond, VA, 23298, USA.
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Garcia Garcia de Paredes A, Rodriguez de Santiago E, Rodriguez-Escaja C, Iborra M, Algaba A, Cameo JI, de la Peña L, Gomollon F, Van Domselaar M, Busta R, Castaño Garcia A, Del Val A, Bermejo F, Gutierrez A, Guardiola J, Mesonero F, Riestra S, Nos P, Albillos A, Lopez-Sanroman A. Idiopathic acute pancreatitis in patients with inflammatory bowel disease: A multicenter cohort study. Pancreatology 2020; 20:331-337. [PMID: 32165149 DOI: 10.1016/j.pan.2020.02.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/02/2020] [Accepted: 02/14/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Idiopathic acute pancreatitis (IAP) in patients with inflammatory bowel disease (IBD) is not well characterized. Our purpose was to better understand this condition and its natural history. METHODS Retrospective cohort study conducted at nine Spanish IBD referral centers. Patients with IBD and a first episode of acute pancreatitis (AP) between 1998 and 2018 were included. Patients with a previous episode of AP or a diagnosis of chronic pancreatitis were excluded. IAP and non-IAP were compared by multivariate logistic regression and survival analysis. RESULTS We identified 185 patients with IBD (68.7% Crohn's disease) and a first episode of AP. Thirty-eight of those 185 (20.6%) fulfilled criteria for IAP. There were no severe cases of IAP. On multivariate analysis, AP before IBD diagnosis (21.1% vs. 3.4%, p = 0.04) and ulcerative colitis (52.6% vs. 23.1%, p = 0.002) were significantly more common in IAP. Further work-up was performed in 16/38 (42%) IAP patients, and a cause was identified in 6/16 (37.5%). Median time from AP to the end of follow-up was 6.3 years (3.1-10). Five-year risk of AP recurrence was significantly higher in IAP group (28% vs. 5.1%, log-rank p = 0.001), with a median time to first recurrence of 4.4 months (2.9-12.2). CONCLUSIONS IAP represents the second cause of AP in patients with IBD. It is more frequent in ulcerative colitis, and presents a high risk of recurrence. Additional imaging work-up after a first episode of IAP in IBD patients is highly advisable, as it identifies a cause in more than one-third of cases.
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Affiliation(s)
- Ana Garcia Garcia de Paredes
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Biosanitaria (IRYCIS), Madrid, Spain.
| | - Enrique Rodriguez de Santiago
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Biosanitaria (IRYCIS), Madrid, Spain
| | - Carlos Rodriguez-Escaja
- Gastroenterology and Hepatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Marisa Iborra
- Gastroenterology and Hepatology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| | - Alicia Algaba
- Gastroenterology Department, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), Madrid, Spain
| | - Jose Ignacio Cameo
- Gastroenterology and Hepatology Department, Hospital General Universitario de Alicante, Alicante, Spain
| | - Luisa de la Peña
- Gastroenterology and Hepatology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain
| | - Fernando Gomollon
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain; Gastroenterology and Hepatology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Manuel Van Domselaar
- Gastroenterology and Hepatology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Spain
| | - Reyes Busta
- Gastroenterology and Hepatology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Andres Castaño Garcia
- Gastroenterology and Hepatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Adolfo Del Val
- Gastroenterology and Hepatology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Fernando Bermejo
- Gastroenterology Department, Hospital Universitario de Fuenlabrada, Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), Madrid, Spain
| | - Ana Gutierrez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain; Gastroenterology and Hepatology Department, Hospital General Universitario de Alicante, Alicante, Spain
| | - Jordi Guardiola
- Gastroenterology and Hepatology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain
| | - Francisco Mesonero
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Biosanitaria (IRYCIS), Madrid, Spain
| | - Sabino Riestra
- Gastroenterology and Hepatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria Del Principado de Asturias (ISPA), Oviedo, Spain
| | - Pilar Nos
- Gastroenterology and Hepatology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| | - Agustin Albillos
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Biosanitaria (IRYCIS), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| | - Antonio Lopez-Sanroman
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Biosanitaria (IRYCIS), Madrid, Spain
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Akhmedov VA, Gaus OV. [Pancreatic diseases and inflammatory bowel diseases: a random or regular combination?]. TERAPEVT ARKH 2020; 92:76-81. [PMID: 32598667 DOI: 10.26442/00403660.2020.01.000463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 11/22/2022]
Abstract
Pathology of the pancreas in inflammatory bowel disease (IBD) is more common than in the general population and includes a wide range of manifestations from asymptomatic to severe disorders. Acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, exocrine pancreatic insufficiency, increased pancreatic enzymes and structural duct anomalies are often associated with IBD. They can be either a manifestation of IBD itself or develop independently.
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Fousekis FS, Theopistos VI, Katsanos KH, Christodoulou DK. Pancreatic Involvement in Inflammatory Bowel Disease: A Review. J Clin Med Res 2018; 10:743-751. [PMID: 30214645 PMCID: PMC6135003 DOI: 10.14740/jocmr3561w] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multisystemic disease, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases in Crohn’s disease and ulcerative colitis is more frequent compared to the general population. Pancreatic manifestations in IBD include a wide heterogenic group of disorders and abnormalities of the pancreas and range from mild self-limited diseases to severe disorders. Acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, pancreatic autoantibodies, exocrine pancreatic insufficiency and asymptomatic imaging and laboratory abnormalities are included in related-IBD pancreatic manifestations. Involvement of the pancreas in IBD may be the result of IBD itself or of medications used.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical School of Ioannina, Greece
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5
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Abstract
PURPOSE OF REVIEW The obesity pandemic poses a unique set of problems for acute pancreatitis - both by increasing acute pancreatitis incidence, and worsening acute pancreatitis severity. This review explores these associations, underlying mechanisms, and potential therapies. RECENT FINDINGS We review how the obesity associated increase in gallstones, surgical, and endoscopic interventions for obesity management, diabetes, and related medications such as incretin-based therapies and hypertriglyceridemia may increase the incidence of acute pancreatitis. The mechanism of how obesity may increase acute pancreatitis severity are discussed with a focus on cytokines, adipokines, damage-associated molecular patterns and unsaturated fatty acid-mediated lipotoxicity. The role of obesity in exacerbating pancreatic necrosis is discussed; focusing on obesity-associated pancreatic steatosis. We also discuss how peripancreatic fat necrosis worsens organ failure independent of pancreatic necrosis. Last, we discuss emerging therapies including choice of intravenous fluids and the use of lipase inhibitors which have shown promise during severe acute pancreatitis. SUMMARY We discuss how obesity may contribute to increasing acute pancreatitis incidence, the role of lipolytic unsaturated fatty acid release in worsening acute pancreatitis, and potential approaches, including appropriate fluid management and lipase inhibition in improving acute pancreatitis outcomes.
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6
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Kim JW, Hwang SW, Park SH, Song TJ, Kim MH, Lee HS, Ye BD, Yang DH, Kim KJ, Byeon JS, Myung SJ, Yang SK. Clinical course of ulcerative colitis patients who develop acute pancreatitis. World J Gastroenterol 2017; 23:3505-3512. [PMID: 28596686 PMCID: PMC5442086 DOI: 10.3748/wjg.v23.i19.3505] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Revised: 03/17/2017] [Accepted: 04/12/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis.
METHODS We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients.
RESULTS Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent.
CONCLUSION Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent.
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Antonini F, Pezzilli R, Angelelli L, Macarri G. Pancreatic disorders in inflammatory bowel disease. World J Gastrointest Pathophysiol 2016; 7:276-282. [PMID: 27574565 PMCID: PMC4981767 DOI: 10.4291/wjgp.v7.i3.276] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 07/08/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD.
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8
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Noel P, Patel K, Durgampudi C, Trivedi RN, de Oliveira C, Crowell MD, Pannala R, Lee K, Brand R, Chennat J, Slivka A, Papachristou GI, Khalid A, Whitcomb DC, DeLany JP, Cline RA, Acharya C, Jaligama D, Murad FM, Yadav D, Navina S, Singh VP. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. Gut 2016; 65:100-11. [PMID: 25500204 PMCID: PMC4869971 DOI: 10.1136/gutjnl-2014-308043] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 11/17/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. METHODS We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. RESULTS NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. CONCLUSIONS UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.
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Affiliation(s)
- Pawan Noel
- Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA
| | - Krutika Patel
- Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA
| | - Chandra Durgampudi
- Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA
| | - Ram N Trivedi
- Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA
| | | | | | - Rahul Pannala
- Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA
| | - Kenneth Lee
- Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Randall Brand
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jennifer Chennat
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Adam Slivka
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Asif Khalid
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David C Whitcomb
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - James P DeLany
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Rachel A Cline
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Chathur Acharya
- Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA
| | - Deepthi Jaligama
- Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA
| | - Faris M Murad
- Departments of Medicine, Washington University, Saint Louis, Missouri, USA
| | - Dhiraj Yadav
- Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Sarah Navina
- Departments of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Vijay P Singh
- Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA
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Ramos LR, Sachar DB, DiMaio CJ, Colombel JF, Torres J. Inflammatory Bowel Disease and Pancreatitis: A Review. J Crohns Colitis 2016; 10:95-104. [PMID: 26351384 DOI: 10.1093/ecco-jcc/jjv153] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 08/19/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Pancreatic abnormalities are common in inflammatory bowel disease (IBD) patients and represent a heterogeneous group of conditions that include acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis and asymptomatic abnormalities. We sought to review the available evidence concerning the aetiology, clinical presentation, diagnosis and treatment of pancreatic conditions in IBD patients. METHODS A PubMed/Medline query was conducted addressing pancreatic disorders in IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Relevant manuscripts about pancreatic disorders in patients with IBD were selected and reviewed. RESULTS Thiopurines and gallstones are the most frequent causes of acute pancreatitis in IBD patients. Thiopurine-induced acute pancreatitis is usually uncomplicated and self-limited. Some evidence suggests that chronic pancreatitis may be more common in IBD. Most cases are idiopathic, affecting young males and patients with ulcerative colitis. Autoimmune pancreatitis is a relatively newly recognized disease and is increasingly diagnosed in IBD, particularly for type 2 autoimmune pancreatitis in ulcerative colitis patients. Asymptomatic exocrine insufficiency, pancreatic duct abnormalities and hyperamylasaemia have been identified in up to 18% of IBD patients, although their clinical significance and relationship with IBD remain undefined. CONCLUSIONS The wide spectrum of pancreatic manifestations in IBD is growing and may represent a challenge to the clinician. A collaborative approach with a pancreas specialist may be the most productive route to determine aetiology, guide additional diagnostic workup, illuminate the aetiology and define the treatment and follow-up of these patients.
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Affiliation(s)
- Lídia Roque Ramos
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - David B Sachar
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Christopher J DiMaio
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Jean-Frédéric Colombel
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Joana Torres
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
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Gregory MH, Henderson A, Klostermeyer K, Esmadi M, Yousef M, Ewing D, Braudis KM, Katta N. Recurrent pancreatitis, rash, and diarrhea: Crohn's disease. Am J Med 2015; 128:133-6. [PMID: 25448173 DOI: 10.1016/j.amjmed.2014.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 10/14/2014] [Accepted: 10/15/2014] [Indexed: 11/27/2022]
Affiliation(s)
| | | | | | - Mohammad Esmadi
- Department of Medicine, University of Missouri School of Medicine, Columbia
| | - Mohamed Yousef
- Department of Medicine, University of Missouri School of Medicine, Columbia
| | - David Ewing
- Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia
| | - Kara M Braudis
- Department of Dermatology, University of Missouri School of Medicine, Columbia
| | - Natraj Katta
- Department of Medicine, University of Missouri School of Medicine, Columbia.
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Abstract
Alcohol and gallstones are the most common etiologic factors in acute pancreatitis (AP). Recurrent AP can lead to chronic pancreatitis (CP). Although the underlying pathophysiology of the disease is complex, immune cells are critical in the pathogenesis of pancreatitis and determining disease severity. In this review, we discuss the role of innate and adaptive immune cells in both AP and CP, potential immune-based therapeutic targets, and animal models used to understand our knowledge of the disease. The relative difficulty of obtaining human pancreatic tissue during pancreatitis makes animal models necessary. Animal models of pancreatitis have been generated to understand disease pathogenesis, test therapeutic interventions, and investigate immune responses. Although current animal models do not recapitulate all aspects of human disease, until better models can be developed available models are useful in addressing key research questions. Differences between experimental and clinical pancreatitis need consideration, and when therapies are tested, models with established disease ought to be included.
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12
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Kambhampati S, Park W, Habtezion A. Pharmacologic therapy for acute pancreatitis. World J Gastroenterol 2014; 20:16868-16880. [PMID: 25493000 PMCID: PMC4258556 DOI: 10.3748/wjg.v20.i45.16868] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 07/23/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.
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13
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Li J, Yang WJ, Huang LM, Tang CW. Immunomodulatory therapies for acute pancreatitis. World J Gastroenterol 2014; 20:16935-16947. [PMID: 25493006 PMCID: PMC4258562 DOI: 10.3748/wjg.v20.i45.16935] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/24/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis.
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14
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Hypothermia slows sequential and parallel steps initiated during caerulein pancreatitis. Pancreatology 2014; 14:459-64. [PMID: 25459565 DOI: 10.1016/j.pan.2014.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Revised: 06/17/2014] [Accepted: 06/23/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Multiple deleterious signaling cascades are simultaneously activated in acute pancreatitis (AP), which may limit the success of pharmacologic approaches targeting a single step. We explored whether cooling acinar cells slows distinct steps initiated from a stimulus causing pancreatitis simultaneously, and the temperature range over which inhibition of such deleterious signaling occurs. METHODS Caerulein (100 nM) induced trypsinogen activation (TGA), CXCL1, CXCL2 mRNA levels, cell injury were studied at 37 °C, 34 °C, 31 °C, 29 °C and 25 °C in acinar cells. Trypsin, cathepsin B activities and cathepsin B mediated TGA were studied at 37 °C, 23 °C and 4 °C. RESULTS There was >80% reduction in TGA, CXCL1 and CXCL2 mRNA levels at 29 °C, and in cell injury at 34 °C, compared to those at 37 °C. Trypsin activity, cathepsin B activity and cathepsin B mediated TGA at 23 °C were respectively, 53%, 64% and 26% of that at 37 °C. Acinar cooling to 31 °C reduced LDH leakage even when cooling was initiated an hour after caerulein stimulation at 37 °C. CONCLUSIONS Hypothermia synergistically and simultaneously slows parallel and distinct signaling steps initiated by caerulein, thereby reducing TGA, upregulation of inflammatory mediators and acinar injury.
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Acharya C, Navina S, Singh VP. Role of pancreatic fat in the outcomes of pancreatitis. Pancreatology 2014; 14:403-8. [PMID: 25278311 PMCID: PMC4185152 DOI: 10.1016/j.pan.2014.06.004] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Revised: 06/19/2014] [Accepted: 06/19/2014] [Indexed: 12/11/2022]
Abstract
The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP).The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9-11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis.
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Affiliation(s)
- Chathur Acharya
- Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA
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16
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Zheng L, Xue J, Jaffee EM, Habtezion A. Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma. Gastroenterology 2013; 144:1230-40. [PMID: 23622132 PMCID: PMC3641650 DOI: 10.1053/j.gastro.2012.12.042] [Citation(s) in RCA: 249] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Revised: 12/12/2012] [Accepted: 12/21/2013] [Indexed: 12/22/2022]
Abstract
Immune cells are important in the pathogenesis of acute pancreatitis and determine disease severity. Results from cytokine-based clinical trials for acute pancreatitis have been disappointing, so strategies that target and alter the behavior of infiltrating immune cells require consideration. Recurrent acute pancreatitis can progress to chronic pancreatitis, which is a well-described risk factor for pancreatic ductal adenocarcinoma (PDA). However, most patients with chronic pancreatitis do not develop PDA, and most patients with PDA do not have a history of pancreatitis. Interestingly, chronic pancreatitis and PDA tissues have similarities in their desmoplasia and inflammatory infiltrates, indicating overlapping inflammatory responses. Further studies are needed to determine the differences and similarities of these responses, improve our understanding of PDA pathogenesis, and develop specific immune-based therapies. Immune cells in PDA produce immunosuppressive signals that allow tumors to evade the immune response. Unlike single therapeutic agent studies that block immunosuppressive mechanisms, studies of combination therapies that include therapeutic vaccines have provided promising results.
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Affiliation(s)
- Lei Zheng
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jing Xue
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elizabeth M. Jaffee
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Aida Habtezion
- Stanford University School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, California and The Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Infliximab: protective effect to intestinal barrier function of rat with acute necrosis pancreatitis at early stage. Pancreas 2013; 42:366-7. [PMID: 23407490 DOI: 10.1097/mpa.0b013e31825c5273] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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18
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Abstract
Kawasaki disease can be associated with gastrointestinal complications, including pancreatitis. We describe a child in whom infliximab infusion for intravenous immunoglobulin-resistant Kawasaki disease coincided with marked clinical improvement of the patient's acute pancreatitis.
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Infliximab enhances the therapeutic effectiveness of octreotide on acute necrotizing pancreatitis in rat model. Pancreas 2012; 41:849-54. [PMID: 22450369 DOI: 10.1097/mpa.0b013e31823fbdc3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To investigate the synergistic activity of infliximab to the therapeutic effectiveness of octreotide in a rat model of acute necrotizing pancreatitis (ANP). METHODS Forty Sprague-Dawley rats were randomly divided into sham-operated group (SO), ANP group (ANP), octreotide group (OG), infliximab group (IG), and combination group (CG) (n = 8 in each group). The ANP model was induced by biliopancreatic duct injection with 4.5% of sodium taurocholate solution. Rats of the OG, IG, and CG were given a tail vein injection of octreotide (10 μg/kg), infliximab (8 mg/kg), and infliximab (8 mg/kg), respectively, combined with octreotide (10 μg/kg) at 6 hours after modeling. All rats in each group were killed at 24 hours after modeling. Serum biochemical indicator and partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) of rats were determined. Pathological severity score of organs were evaluated. RESULTS The serum biochemical indicator and organs' pathology score of OG , IG, and CG were obviously lower than those in the ANP group, and those in the CG were the lowest (P < 0.05). The PaO2/FiO2 levels in the OG, IG, and CG were significantly higher than that in the ANP group (P < 0.05). CONCLUSION Infliximab could significantly lower the serum biochemical indicator, improve organs' function, and enhance the therapeutic effectiveness of octreotide on ANP.
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Tang Y, Liao Y, Kawaguchi-Sakita N, Raut V, Fakhrejahani E, Qian N, Toi M. Sinisan, a traditional Chinese medicine, attenuates experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2011; 18:551-8. [PMID: 21234610 DOI: 10.1007/s00534-010-0368-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND/PURPOSE Sinisan, a traditional Chinese medicine, is effective for the treatment of gastrointestinal disorders. In this study, we investigated the potential protective role of Sinisan against chronic pancreatitis (CP) in rats. METHODS CP was induced in rats by intrapancreatic injection of trinitrobenzene sulfonic acid (TNBS). Rats were randomly divided into a sham group, a TNBS-induced CP group and a Sinisan-treated group. Serum amylase and histological score were used to evaluate the severity of disease. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-10 (IL-10) and α-smooth muscle actin (α-SMA) were also measured in the three groups. Mechanical allodynia was measured with von Frey filaments. In addition, the protein levels of nerve growth factor (NGF) were measured in pancreatic tissues. RESULTS Administration of Sinisan significantly decreased the severity of CP. In the Sinisan-treated group, serum amylase, TNF-α, IL-1β, COX-2 and α-SMA levels were lower and the level of IL-10 was upregulated compared with the TNBS-induced CP group. Furthermore, treatment with Sinisan significantly, though not completely, attenuated the allodynia. Simultaneously NGF expression was also significantly downregulated in the Sinisan-treated group compared with the TNBS-induced CP group. CONCLUSIONS Sinisan could be an effective treatment modality for CP via its anti-inflammatory, anti-fibrotic and analgesic properties. It may be a promising drug candidate for the treatment of patients with CP.
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Affiliation(s)
- Yu Tang
- Department of Medical Image Center, Chinese PLA 302 Hospital, Beijing, China
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21
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Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J DERMATOL TREAT 2009; 15:280-94. [PMID: 15370396 DOI: 10.1080/09546630410017275] [Citation(s) in RCA: 226] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
For more than 5 years, infliximab and etanercept have been utilized to treat rheumatoid arthritis and Crohn's disease. There is therefore much post-approval data on their side effects. A variety of Medline searches were done at the beginning of June 2004 using the terms 'etanercept', 'infliximab' and 'adalimumab' and the words 'lymphoma', 'infection', 'congestive heart failure', 'demyelinating disease', 'lupus', 'antibodies', 'injection site reaction', 'systemic', 'side effects' and 'skin'. Approximately 150 articles were so identified. In addition, FDA and manufacturers' data obtained by internet searches using Google were reviewed. The important side effects that have been most extensively related to TNFalpha blockers include: lymphoma, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects. The risk of these side effects is very low. Nevertheless, it is important for clinicians to be aware of these side effects when prescribing therapy.
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Affiliation(s)
- N Scheinfeld
- Department of Dermatology, St Luke's Roosevelt Hospital Center, New York, NY 10025, USA.
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Abstract
The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.
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Abstract
Chronic autoimmune pancreatitis is an entity distinct from all other forms of chronic pancreatitis. It is expressed by signs of acute or chronic pancreatitis, sometimes associated with cholestatic jaundice. In imaging, it may appear as diffuse (duct destructive) or pseudotumoral lesions. These 2 aspects are probably different clinical forms of chronic autoimmune pancreatitis. Some autoimmune diseases are associated with chronic autoimmune pancreatitis, but not consistently. One such disease involves a bile disorder very similar to primary sclerosing cholangitis but responsive to corticosteroid treatment. Pancreatitis may be a sign of intestinal inflammatory diseases (and vice versa): testing for Crohn's disease and ulcerative rectocolitis is justified in patients with idiopathic pancreatitis. Chronic autoimmune pancreatitis must be routinely considered in patients with a pancreatic tumor that is for a clinical, epidemiologic, serologic or imaging reason not completely consistent with pancreatic adenocarcinoma. A short corticosteroid therapy (< 4 weeks) is probably less harmful in a patient with pancreatic adenocarcinoma than pancreatectomy (or chemotherapy) in patients with chronic autoimmune pancreatitis. Diagnosis depends on a body of clinical and radiologic evidence. The diagnostic value of serologic markers and especially of autoantibodies must be clarified in the future.
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Affiliation(s)
- Philippe Lévy
- Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, Clichy, France.
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Ross AS, Gasparaitis A, Hurst R, Hanauer SB, Rubin DT. Superior mesenteric vein thrombosis after colectomy in a patient with Crohn's disease. ACTA ACUST UNITED AC 2005; 2:281-5; quiz 1 p following 285. [PMID: 16265232 DOI: 10.1038/ncpgasthep0195] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2005] [Accepted: 05/05/2005] [Indexed: 01/06/2023]
Abstract
BACKGROUND An 18-year-old woman with a history of Crohn's disease presented in January 2004 with severe epigastric pain, nausea and vomiting of 4 hours' duration. The patient was diagnosed with inflammatory bowel disease, thought to be consistent with ulcerative colitis, in March 2003, but had no medical history up until this point. Initial treatment with mesalamine was unsuccessful and she subsequently presented with medically resistant fulminant colitis and required an urgent colectomy in June 2003. Her immediate postoperative course was uneventful and she was discharged on tapering doses of prednisone. In August 2003, an ileoscopy revealed inflamed, mildly ulcerated mucosa, and biopsies were consistent with Crohn's disease. Azathioprine was added to the treatment regimen and the patient tapered off prednisone. At this stage the patient continued to do well clinically up until presentation. INVESTIGATIONS Small bowel series, abdominal CT scan, abdominal ultrasound, exploratory laparotomy. DIAGNOSIS Acute mesenteric ischemia secondary to superior mesenteric vein thrombosis. MANAGEMENT Resection of necrotic bowel, antibiotics and systemic anticoagulation.
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Affiliation(s)
- Andrew S Ross
- Department of Surgery, University of Chicago, IL, USA
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Carpenter E, Jackson MA, Friesen CA, Scarbrough M, Roberts CC. Crohn's-associated chronic recurrent multifocal osteomyelitis responsive to infliximab. J Pediatr 2004; 144:541-4. [PMID: 15069408 DOI: 10.1016/j.jpeds.2003.12.038] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
We report a case of chronic recurrent clavicular osteomyelitis in association with Crohn disease. Steroid therapy resulted in partial remission; however, intractable shoulder pain and an enlarging clavicular mass subsequently recurred. Infliximab therapy resulted in significant improvement in the degree of bone pain and resolution of the large sclerotic clavicular lesion.
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Affiliation(s)
- Ellen Carpenter
- Inflammatory Bowel Disease Program, Section of Gastroenterology, The Children's Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
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Abstract
PURPOSE Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis of acute pancreatitis and related systemic complications. The aim of this study is to investigate the therapeutic effectiveness of monoclonal TNF antibody (infliximab) in acute edematous and severe necrotizing pancreatitis models in rats. METHODS One hundred rats were randomly divided into 10 groups. Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20 microg/kg 4 times subcutaneously at hourly intervals. Severe necrotizing pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase enzyme activity (MPO), and pulmonary changes were assessed. RESULTS Infliximab treatment significantly decreased serum amylase activity (11939 +/- 1914 U/L versus 3458 +/- 915 U/L, P < 0.001) and histopathologic score (4.1 +/- 0.5 versus 1.5 +/- 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to decrease pathologic score (9.4 +/- 1.2 versus 3.6 +/- 0.8, P < 0.001) and serum amylase activity (20442 +/- 2375 versus 8990 +/- 1730, P < 0.01). It ameliorated both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also alleviated alveolar edema and acute respiratory distress syndrome like pulmonary complications, but the difference was not significant. CONCLUSIONS Chimeric TNF antibody, infliximab, should be evaluated for treatment of acute pancreatitis.
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Affiliation(s)
- Nevin Oruc
- Ege University, Faculty of Medicine, Gastroenterology Department, Izmir, Turkey
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Triantafillidis JK, Cheracakis P, Merikas EG, Peros G. Acute pancreatitis may precede the clinical manifestations of Crohn's disease. Am J Gastroenterol 2003; 98:1210-1211. [PMID: 12809859 DOI: 10.1111/j.1572-0241.2003.07436.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Triantafillidis JK, Cheracakis P. Re: Fefferman et al.--"Recurrence" of chronic pancreatitis appearing on a patient with underlying Crohn's disease. Am J Gastroenterol 2002; 97:761-2. [PMID: 11922579 DOI: 10.1111/j.1572-0241.2002.05567.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Fefferman DS, Alsahli M, Lodhavia PJ, Shah SA, Farrell RJ. Re: Triantafillidis et al.--Acute idiopathic pancreatitis complicating active Crohn's disease: favorable response to infliximab treatment. Am J Gastroenterol 2001; 96:2510-1. [PMID: 11513207 DOI: 10.1111/j.1572-0241.2001.04070.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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