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Pan H, Chen H, Kong W, Ning J, Ge Z, Tian Y, Zou N, Zhu H, Zhang J, Tao Y, Gu Z, Zheng M, Ruan G, Jiang L, Li Z, Huang J, Zhou C, Xu G, Luo Q. Video-Assisted Thoracoscopic Surgery Versus Thoracotomy Following Neoadjuvant Immunochemotherapy in Resectable Stage III Non-Small Cell Lung Cancer Among Chinese Populations: A Multi-Center Retrospective Cohort Study. Clin Lung Cancer 2024; 25:395-406.e5. [PMID: 38705833 DOI: 10.1016/j.cllc.2024.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 02/25/2024] [Accepted: 03/31/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND Immune checkpoint inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment but may pose greater technical challenges for surgery. This study aims to assess the feasibility and oncological effectiveness of video-assisted thoracoscopic surgery (VATS) for resectable stage III NSCLC after neoadjuvant immunochemotherapy. METHODS Initial stage IIIA-IIIB NSCLC patients with neoadjuvant immunochemotherapy undergoing either VATS or open lobectomy at 6 medical centers during 2019-2023 were retrospectively identified. Perioperative outcomes and 2-year survival was analyzed. Propensity-score matching (PSM) was employed to balance patient baseline characteristics. RESULTS Among the total 143 patients, PSM yielded 62 cases each for VATS and OPEN groups. Induction-related adverse events were comparable between the 2 groups. VATS showed a 14.5% conversion rate. Notably, VATS decreased numeric rating scales for postoperative pain, shortened chest tube duration (5[4-7] vs. 6[5-8] days, P = .021), reduced postoperative comorbidities (21.0% vs. 37.1%, P = .048), and dissected less N1 lymph nodes (5[4-6] vs. 7[5-9], P = .005) compared with thoracotomy. Even when converted, VATS achieves perioperative outcomes equivalent to thoracotomy. Additionally, over a median follow-up of 29.5 months, VATS and thoracotomy demonstrated comparable 2-year recurrence-free survival (77.20% vs. 73.73%, P = .640), overall survival (87.22% vs. 88.00%, P = .738), cumulative incidences of cancer-related death, and recurrence patterns. Subsequent subgroup comparisons and multivariate Cox analysis likewise revealed no statistical difference between VATS and thoracotomy. CONCLUSION VATS is a viable and effective option for resectable stage III NSCLC patients following neoadjuvant immunochemotherapy, leading to decreased surgical-related pain, earlier chest tube removal, reduced postoperative complications, and similar survival outcomes compared to thoracotomy.
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Affiliation(s)
- Hanbo Pan
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hang Chen
- Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Weicheng Kong
- Department of Thoracic Surgery, Putuo District People's Hospital, Zhoushan, China
| | - Junwei Ning
- Department of Thoracic Surgery, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhen Ge
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yu Tian
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ningyuan Zou
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongda Zhu
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiaqi Zhang
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yixing Tao
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zenan Gu
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Zheng
- Department of Thoracic Surgery, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guomo Ruan
- Department of Clinical Medicine, Wenzhou People's Hospital, Shanghai University School of Medicine, Wenzhou, China
| | - Long Jiang
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ziming Li
- Department of Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Huang
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Chengwei Zhou
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.
| | - Guodong Xu
- Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
| | - Qingquan Luo
- Department of Thoracic Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Ulevicius J, Jasukaitiene A, Bartkeviciene A, Dambrauskas Z, Gulbinas A, Urboniene D, Paskauskas S. Preoperative Immune Cell Dysregulation Accompanies Ovarian Cancer Patients into the Postoperative Period. Int J Mol Sci 2024; 25:7087. [PMID: 39000195 PMCID: PMC11240929 DOI: 10.3390/ijms25137087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/18/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system's role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.
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Affiliation(s)
- Jonas Ulevicius
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Aldona Jasukaitiene
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Arenida Bartkeviciene
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Zilvinas Dambrauskas
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Antanas Gulbinas
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Daiva Urboniene
- Department of Laboratory Medicine, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania;
| | - Saulius Paskauskas
- Department of Obstetrics and Gynecology, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania
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Ulevicius J, Jasukaitiene A, Bartkeviciene A, Dambrauskas Z, Gulbinas A, Urboniene D, Paskauskas S. Dysregulation of Peripheral Blood Mononuclear Cells and Immune-Related Proteins during the Early Post-Operative Immune Response in Ovarian Cancer Patients. Cancers (Basel) 2023; 16:190. [PMID: 38201617 PMCID: PMC10778568 DOI: 10.3390/cancers16010190] [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: 12/05/2023] [Revised: 12/27/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024] Open
Abstract
Surgical treatment is a cornerstone of ovarian cancer (OC) therapy and exerts a substantial influence on the immune system. Immune responses also play a pivotal and intricate role in OC progression. The aim of this study was to investigate the dynamics of immune-related protein expression and the activity of peripheral blood mononuclear cells (PBMCs) in OC patients, both before surgery and during the early postoperative phase. The study cohort comprised 23 OC patients and 20 non-cancer controls. A comprehensive analysis of PBMCs revealed significant pre-operative downregulation in the mRNA expression of multiple immune-related proteins, including interleukins, PD-1, PD-L1, and HO-1. This was followed by further dysregulation during the first 5 post-operative days. Although most serum interleukin concentrations showed only minor changes, a distinct increase in IL-6 and HO-1 levels was observed post-operatively. Reduced metabolic and phagocytic activity and increased production of reactive oxygen species (ROS) were observed on day 1 post-surgery. These findings suggest a shift towards immune tolerance during the early post-operative phase of OC, potentially creating a window for treatment. Further research into post-operative PBMC activity could lead to the development of new or improved treatment strategies for OC.
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Affiliation(s)
- Jonas Ulevicius
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Aldona Jasukaitiene
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Arenida Bartkeviciene
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Zilvinas Dambrauskas
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Antanas Gulbinas
- Laboratory of Surgical Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania; (A.J.); (A.B.); (Z.D.); (A.G.)
| | - Daiva Urboniene
- Department of Laboratory Medicine, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania;
| | - Saulius Paskauskas
- Department of Obstetrics and Gynecology, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus g. 9, LT-44307 Kaunas, Lithuania;
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Ding C, Jia Q, Wu Z, Zhang Y, Hu Y, Wang J, Wei D. Efficacy of thoracoscopic segmentectomy versus lobectomy in the treatment of early invasive lung adenocarcinoma: a propensity score matching study. Front Oncol 2023; 13:1186991. [PMID: 37719018 PMCID: PMC10502230 DOI: 10.3389/fonc.2023.1186991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 08/16/2023] [Indexed: 09/19/2023] Open
Abstract
Objective This study aimed to investigate and analyze the clinical application value of thoracoscopic segmentectomy and lobectomy in patients with invasive pulmonary adenocarcinoma. Methods 286 patients with invasive pulmonary adenocarcinoma who underwent segmentectomy or lobectomy at the First Hospital of Jiaxing City from January 2018 to June 2020 were retrospectively analyzed. Patients were divided into a thoracoscopic segmentectomy group(n=97) and a lobectomy group (n=189). Patients were compared after obtaining 1:1 propensity score-matched cohorts. Outcome indicators included surgery-related indicators, immune-inflammation-related indicators, postoperative complications, recurrence, and metastasis. Results After 1:1 propensity score matching, 93 patients were included in each group. We found that the volume of intraoperative blood loss in the segmentectomy group was significantly less than in the lobectomy group (P=0.014). The duration of postoperative drainage (P = 0.005) and hospitalization (P=0.002) in the segmentectomy group were significantly shorter than in the lobectomy group. In terms of immunoinflammatory response, compared with the lobectomy group, white blood cells, neutrophils, SII, and NLR in the segmentectomy group were significantly lower than in the lobectomy group (P< 0.05). The recurrence-free survival (RFS) rates in the segmentectomy and lobectomy were 80.5% and 88.2% at 1 year and 35.1% and 52.6% at 3 years, respectively, and the difference was statistically significant (P<0.05). The segmentectomy group achieved similar outcomes to the lobectomy group at 1 year and 3 years (P > 0.05). Multivariate COX regression analysis showed that CAR was an independent risk factor for RFS in patients undergoing invasive adenocarcinoma surgery. Conclusion Compared with lobectomy, thoracoscopic segmentectomy can effectively reduce the postoperative inflammatory response in patients with early invasive lung adenocarcinoma and promote patient recovery. Although segmentectomy is associated with a higher recurrence rate in the short term for patients with early invasive lung adenocarcinoma, the associated survival rate is similar to the lobectomy group. Segmentectomy should be considered in the treatment of early invasive lung adenocarcinoma. Meanwhile, postoperative CAR represents an independent risk factor for early postoperative recurrence in patients with IAC.
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Affiliation(s)
- Congyi Ding
- Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, China
| | - Qiyu Jia
- Department of Trauma Orthopedics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Zhongjie Wu
- Department of Cardiothoracic Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Yanfei Zhang
- Department of Cardiothoracic Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Yi Hu
- Department of Cardiothoracic Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Jingyu Wang
- Department of Cardiothoracic Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Dahai Wei
- Department of Cardiothoracic Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
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Pan H, Zou N, Huang J, Tian Y, Jia Y, Zhu H, Gu Z, Jiang L, Yao F, Luo Q. Short- and medium-term outcomes of video-assisted thoracoscopic surgery versus thoracotomy for carinal lung resection combined with carina reconstruction in locally advanced non-small cell lung cancer patients. Thorac Cancer 2023. [PMID: 37127879 DOI: 10.1111/1759-7714.14919] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/15/2023] [Accepted: 04/17/2023] [Indexed: 05/03/2023] Open
Abstract
BACKGROUND The application of video-assisted thoracoscopic surgery (VATS) for complex carina surgeries in treating non-small cell lung cancer (NSCLC) patients with involved carina is controversial. This study compared short- and medium-term outcomes of VATS versus thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC, aiming to assess the potential benefit of VATS over thoracotomy for these patients. METHODS A total of 37 consecutive NSCLC cases receiving VATS (n = 14) or thoracotomy (n = 23) for carinal lung resection with carina reconstruction from 2016 to 2021 were retrospectively identified. Baseline clinicopathological characteristics, perioperative outcomes, and survival profiles were investigated. RESULTS Patients in the VATS and thoracotomy groups had comparable baseline clinicopathological characteristics (all p > 0.050). VATS decreased postoperative drainage volume compared with thoracotomy (1280 [1170-1510] vs. 1795 [1510-1905] mL, p = 0.012). Regarding surgical-related pains, VATS reduced numeric rating scale scores on the postoperative day 1 (4 [3, 4] vs. 5 [4, 5], p = 0.021) and day 2 (3 [3, 4] vs. 5 [3-5], p = 0.023) than thoracotomy. No difference was found between the VATS and thoracotomy groups in other perioperative outcomes, postoperative complications, and assessment of lymph nodes (LNs) and LN stations (all p > 0.050). Moreover, patients in the two groups had comparable 3-year disease-free survival (DFS), overall survival (OS), and recurrence and mortality patterns. Further subgroup and Cox hazards regression analyses also observed no difference in DFS or OS between the two groups. CONCLUSIONS VATS reduced postoperative drainage volume and ameliorated surgical-related pain, and achieved comparable medium-term survival compared to thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC.
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Affiliation(s)
- Hanbo Pan
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ningyuan Zou
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Huang
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Tian
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yunxuan Jia
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongda Zhu
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zenan Gu
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Long Jiang
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Feng Yao
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingquan Luo
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yuan JL, Kang K, Li B, Lu J, Miao MR, Kang X, Zhang JQ, Zhang W. The Effects of Sevoflurane vs. Propofol for Inflammatory Responses in Patients Undergoing Lung Resection: A Meta-Analysis of Randomized Controlled Trials. Front Surg 2021; 8:692734. [PMID: 34277696 PMCID: PMC8282814 DOI: 10.3389/fsurg.2021.692734] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 05/31/2021] [Indexed: 01/14/2023] Open
Abstract
Objective: Inflammatory cytokines are increased during one-lung ventilation in patients undergoing lung resection, and this increase can be fatal. Propofol and sevoflurane are the main anesthetics used for these patients. Unfortunately, there is no consensus on the best choice of an anesthetic agent concerning an inflammatory response in patients undergoing lung resection. This meta-analysis aimed to compare the effects of propofol and sevoflurane on the inflammatory response in patients undergoing lung resection. Methods: We searched electronic databases to identify randomized controlled trials comparing the effects of different anesthetics (sevoflurane vs. propofol) on the inflammatory response. The primary outcome concerned the concentration of systemic inflammatory cytokines. The secondary outcomes concerned the concentrations of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid from the dependent and independent lung. Random effects analysis of the meta-analyses were performed to synthesize the evidence and to assess the concentrations of inflammatory factors in the sevoflurane and propofol groups. Results: Eight trials involving 488 participants undergoing lung resection with one-lung ventilation were included. There was no significant difference in the concentrations of systemic interleukin (IL)-6, IL-10, or tumor necrosis factor α between the sevoflurane and propofol groups. Compared with the propofol group, BAL levels of IL-6 in the dependent ventilated lung were decreased in the sevoflurane group (three trials, 256 participants; standardized mean difference [SMD], −0.51; 95% confidence interval [CI], −0.90 to −0.11; p = 0.01; I2 = 46%). The BAL levels of IL-6 in the independent ventilated lung were also decreased by sevoflurane (four trials, 362 participants; SMD, −0.70; 95% [CI], −0.93 to −0.47; p < 0.00001; I2 = 0%). Conclusions: There was no difference in the systemic inflammatory response between the sevoflurane and propofol groups. However, compared with propofol, sevoflurane can reduce the local alveolar inflammatory response. Additional research is necessary to confirm whether the inflammatory response is direct or indirect.
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Affiliation(s)
- Jing-Li Yuan
- Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Kang Kang
- Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Bing Li
- Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Jie Lu
- Department of Health Statistics, School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Meng-Rong Miao
- Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xia Kang
- Department of Anesthesiology and Perioperative Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Jia-Qiang Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Wei Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
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Zhao JL, Nie YQ, Yang P, Jiang DZ, Zhang FW. Effect of selective lymph node dissection on immune function in patients with T1 stage non-small cell lung cancer: a randomized controlled trial. Transl Cancer Res 2021; 10:2918-2931. [PMID: 35116601 PMCID: PMC8797331 DOI: 10.21037/tcr-21-524] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/22/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Many lymph nodes resected from early-stage non-small cell lung cancer (NSCLC) patients haven't metastasis. Selective lymph node dissection (SLND) can reduce surgical trauma by retaining non-metastatic lymph nodes, we aimed to investigate whether SLND could reduce immune impairment compared with systematic lymph node dissection. METHODS According to the selection criteria, patients with no metastasis in hilar and regional lymph nodes were selected as the research subjects. The patients were randomly divided into 2 groups: the SLND group (Group SD) and the systematic lymph node dissection group (Group CD). At 24 hours before surgery and on the 1st and 3rd postoperative days (POD), fasting venous blood was sampled to detect cytokine indicators [interleukin-6 (IL-6), C-reactive protein (CRP)], cellular immune indicators [lymphocytes, natural killer cells (NK cells), CD4+, CD8+, CD4+/CD8+], and humoral immune indicators (IgG, IgA, IgM). At the same time, clinically indicators of the patients were recorded. All indicators between the 2 groups were compared. RESULTS The comparison of clinical indicators between the two groups showed that SLND is more conducive to patients' rapid recovery after surgery. CRP and IL-6 levels in Group CD were significantly higher than those in Group SD after surgery (P<0.05). There were no statistical differences between the 2 groups in the proportions of lymphocytes and NK cells after surgery (P>0.05). The proportions of CD4+ cells and CD4+/CD8+ in Group CD were significantly lower than those in Group SD at POD1 (P<0.05). The proportion of CD8+ cells was significantly higher in Group CD than in Group SD at POD3 (P<0.05). There were no significant differences in IgG, IgA, and IgM levels between the 2 groups at the same point in time (P>0.05). CONCLUSIONS Compared with systematic lymph node dissection, SLND has the following advantages: (I) it is more conducive to patients' rapid recovery after surgery; (II) it can reduce the body's acute inflammatory response and non-specific immune damage; (III) it can reduce the damage to cellular immune function caused by surgery. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2100045893.
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Affiliation(s)
- Jin-Long Zhao
- Department of Thoracic Surgery, Linyi People’s Hospital, Linyi, China
| | - Yun-Qiang Nie
- Department of Respiratory and Critical Care, Linyi People’s Hospital, Linyi, China
| | - Peng Yang
- Department of Thoracic Surgery, Linyi People’s Hospital, Linyi, China
| | - Da-Zhi Jiang
- Department of Thoracic Surgery, Linyi People’s Hospital, Linyi, China
| | - Feng-Wei Zhang
- Department of Cardiac Surgery, Linyi People’s Hospital, Linyi, China
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Corsini EM, Wang Q, Tran HT, Mitchell KG, Antonoff MB, Hofstetter WL, Mehran RJ, Rice DC, Roth JA, Swisher SG, Vaporciyan AA, Walsh GL, Reuben A, Vasquez ME, Bernatchez C, Wang J, Cascone T, Zhang J, Heymach JV, Gibbons DL, Haymaker CL, Sepesi B. Peripheral cytokines are not influenced by the type of surgical approach for non-small cell lung cancer by four weeks postoperatively. Lung Cancer 2020; 146:303-309. [PMID: 32619781 DOI: 10.1016/j.lungcan.2020.06.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/08/2020] [Accepted: 06/18/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVES The influence of surgical approach on systemic inflammatory response and the subsequent oncologic impact for non-small cell lung cancer is debated. We aimed to measure the effects of thoracic surgical approach on peripheral cytokine milieu over time. METHODS Patients undergoing primary lung resection without neoadjuvant therapy (2016-2018) were evaluated. A panel of 43 cytokines, angiogenic factors, and inflammatory molecules (CAFs) were evaluated in peripheral blood preoperatively, at 24 -hs and 4-weeks postoperatively. Differences between CAFs in patients undergoing thoracotomy versus video-assisted thoracoscopic surgery (VATS) at all timepoints were assessed using Student's t-test. RESULTS 76 patients with available peripheral CAF panels met inclusion criteria. Thoracotomy was performed in 53 (70 %) patients while VATS was undertaken in 23 (30 %). Upon examination of known inflammatory CAFs, including IL-1β, IL-6, IL-8, IL-10, IFN-γ, and soluble (s) CD27, no differences were detected at 24 h or 4 weeks postoperatively between surgical groups. Examination of trends over time did not demonstrate any temporal derangements for these CAFs, with return to baseline levels by 4 weeks postoperatively for both groups. Evaluation of soluble (s) checkpoint molecules, including sPD-1, sPD-L1, sTIM-3, and sCTLA-4, did not reveal any differences in the immediate postoperative or long-term recovery period. CONCLUSIONS Peripheral immune profiles following pulmonary resection do not appear to differ between VATS and thoracotomy postoperatively. CAF fluctuations are transient and recover rapidly. These results, at the peripheral cytokine level, suggest that the surgical approach for lung cancer is unlikely to alter the effectiveness of novel immune-modulating systemic therapies, although more studies are needed to validate these findings.
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Affiliation(s)
- Erin M Corsini
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Qi Wang
- Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Hai T Tran
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Kyle G Mitchell
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Mara B Antonoff
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Reza J Mehran
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - David C Rice
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Jack A Roth
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Stephen G Swisher
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Ara A Vaporciyan
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Garrett L Walsh
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
| | - Alexandre Reuben
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Mayra E Vasquez
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Chantale Bernatchez
- Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jing Wang
- Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Tina Cascone
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jianjun Zhang
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - John V Heymach
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Don L Gibbons
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Cara L Haymaker
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States.
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9
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Lee HM, Ghill BK, Park E, Park CY, Choi WK, Lee J. Changes in the Ratio of T Helper 1 to T Helper 2 Signature Cytokines in Patients Undergoing Living Donor Liver Transplantation Surgery: A Prospective Controlled Study. Transplant Proc 2018; 50:3621-3625. [DOI: 10.1016/j.transproceed.2018.08.055] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 07/30/2018] [Accepted: 08/16/2018] [Indexed: 01/18/2023]
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10
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Hwang W, Lee J. Pathophysiologic Implications of Cytokines Secretion during Liver Transplantation Surgery. Int J Med Sci 2018; 15:1737-1745. [PMID: 30588198 PMCID: PMC6299421 DOI: 10.7150/ijms.28382] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 10/18/2018] [Indexed: 12/29/2022] Open
Abstract
We introduce the following issues of the cytokines secretion during liver transplantation surgery in this review article; 1) the aspect of cytokines secretion during liver transplantation surgery, 2) the evidences of association of cytokines concentration with post-transplantation graft survival, 3) a variety of factors that may influence the secretion of cytokines during liver transplantation, 4) pro-inflammatory and anti-inflammatory cytokine balance during the surgery, and 5) the issues of T helper 1 and T helper 2, and T helper 17 and regulatory T cell signature cytokines secretion and their ratio during liver transplantation surgery. Primary failure of the liver is associated with the secondary dysfunction of virtually all other organ systems, including the cardiovascular, pulmonary, renal, coagulation and central nervous systems. In addition, liver transplantation surgery itself is a major surgical procedure with accompanying life-threatening hemorrhage, massive transfusion, clamping and unclamping of great vessels and resulting ischemia-reperfusion injury and cardiovascular instability. Both the underlying liver failure and the surgical events act as stressors and promote the secretion of various cytokines. So it is clinically important to understand above issues regarding the cytokines secretion during liver transplantation surgery. As cytokines secretion has clear relationship with post-transplantation clinical outcomes, future study directions for artificially manipulating cytokines secretion is also suggested for enhancing outcomes of the patients.
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Affiliation(s)
- Wonjung Hwang
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Jaemin Lee
- Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea
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11
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Lee JM, Han HJ, Choi WK, Yoo S, Baek S, Lee J. Immunomodulatory effects of intraoperative dexmedetomidine on T helper 1, T helper 2, T helper 17 and regulatory T cells cytokine levels and their balance: a prospective, randomised, double-blind, dose-response clinical study. BMC Anesthesiol 2018; 18:164. [PMID: 30409131 PMCID: PMC6225705 DOI: 10.1186/s12871-018-0625-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 10/22/2018] [Indexed: 12/21/2022] Open
Abstract
Background The ratio of T helper 1 (Th1) to T helper 2 (Th2) as well as T helper 17 (Th17) to regulatory T cells (Treg) represents the state and direction of immune response. Recent studies demonstrated that dexmedetomidine reduced the secretion of inflammatory cytokines. We performed this study to investigate the effect of different doses of intraoperative dexmedetomidine on the expression of Th1, Th2, T17 and Treg cytokines and their ratios. Methods Seventy-five patients undergoing laparoscopic cholecystectomy were randomly separated into one of three groups: the full dose group (n = 25), in which dexmedetomidine was infused with a 1.0 μg/kg loading followed by an infusion of 0.5 μg/kg/min after anaesthetic induction, or the half dose group (n = 26), in which the dose was half of that of full dose group, or the saline group (n = 24) which was control. T cell cytokines were quantified by sandwich enzyme-linked immunoassay for blood samples taken after anaesthetic induction (T0), at the end of surgery (T1), and 60 min after surgery (T2). IFN-gamma/IL-4 and IL-17/IL-10, which represent the ratio of Th1/Th2 and Th17/Treg cytokines, respectively, were calculated as indices of immune cell levels based upon serum cytokines levels in place of direct measurements. C-reactive protein (CRP) concentrations were measured on the next day following surgery. Results The full dose group was associated with higher ratios of IFN-gamma/IL-4 than those of half dose group and control [10.1 vs. 1.9 at T1 (P = 0.041) compared with half dose group, and 10.1 vs. 0.2 at T1 (P = 0.031), 7.4 vs. 0.1 at T2 (P = 0.025) compared with control]. IL-17/IL-10 ratios were higher in the full dose group than those in control [4.2 vs. 0.6 at T1 (P = 0.013), 3.0 vs. 0.3 at T2 (P = 0.011)]. The CRP levels were lower in the dexmedetomidine-treated groups in a dose-dependent manner. Conclusions Dexmedetomidine exhibits immunomodulatory effects, shifting the Th1/Th2 and T17/Treg cytokine balance toward Th1 and T17, respectively, in a dose-dependent pattern in patients with surgical and anaesthetic stress. Trial registration Clinical Research Information Service, Republic of Korea (CRIS); KCT0000503; Registration date: Aug 13, 2012.
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Affiliation(s)
- Jae-Myeong Lee
- Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Choenbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Hyo-Jo Han
- Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
| | - Won-Kyu Choi
- Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Choenbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Subin Yoo
- Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Choenbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Soojin Baek
- Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Choenbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Jaemin Lee
- Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Choenbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea.
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12
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Angka L, Khan ST, Kilgour MK, Xu R, Kennedy MA, Auer RC. Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery. Int J Mol Sci 2017; 18:ijms18081787. [PMID: 28817109 PMCID: PMC5578175 DOI: 10.3390/ijms18081787] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 08/13/2017] [Accepted: 08/14/2017] [Indexed: 02/06/2023] Open
Abstract
The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines), anti-inflammatory cytokines (e.g., IL-6, TGF-β), and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery.
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Affiliation(s)
- Leonard Angka
- Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
| | - Sarwat T Khan
- Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
| | - Marisa K Kilgour
- Deeley Research Centre, BC Cancer Agency, Victoria, BC V8R 6V5, Canada.
| | - Rebecca Xu
- Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
| | - Michael A Kennedy
- Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
| | - Rebecca C Auer
- Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
- Department of Surgery, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
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13
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Feng C, Feng M, Jiao R, Liu D, Jin Y, Zhao X, Xiao R. Effect of Dezocine on IL-12 and IL-10 secretion and lymphocyte activation by culturing dendritic cells from human umbilical cord blood. Eur J Pharmacol 2016; 796:110-114. [PMID: 28017828 DOI: 10.1016/j.ejphar.2016.12.035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 12/20/2016] [Accepted: 12/21/2016] [Indexed: 01/06/2023]
Abstract
Dezocine has been generally utilized for pain therapy and auxiliary anesthesia. Although it has some advantages on the prevention of some anesthesia related complications, its effect on immune responses remains unclear. Our study investigated the effects of Dezocine on IL-10 and IL-12 secretion and lymphocytes activation by culturing dendritic cells (DCs), and revealed the underlying mechanism. Mononuclear cells were divided into negative control group (GN), positive control group (GP), experimental group (GD; GD5, D7, D9). DCs morphological structure was performed by microscope and its phenotypes were evaluated by flow cytometry. IL-12 and IL-10 levels were determined by ELISA and lymphocyte proliferation capacity was performed by MTT assay. Results showed that typical morphological characters of DCs were observed in GP and GD. The positive cell percentages of CD83, HLA-DR, CD80, CD86 and CD40 in GD were lower than those in GP, but higher than the GN group (P<0.01). IL-12 level in GD was higher than in GP, however, IL-10 was opposite (P<0.01). The optical density in GD was lower than in GP (P<0.05). There were no dose-dependent relationships correlated with DCs phenotypes, IL-12 and IL-10 secretion and lymphocytes activation (P>0.05). Our conclusion was that Dezocine might play a role in immunity by regulating IL-12 and IL-10 secretion, and affecting lymphocyte activity in process of DCs maturation. Our findings reveal an unexpected immuno-regulatory function of Dezocine in DCs and provide an important insight for investigating the effect of opioid drugs in immunologic responses.
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Affiliation(s)
- Chang Feng
- Department of Anesthesiology, The Second Hospital of Shandong University, 247 Bei Yuan Street, Jinan 250033, China
| | - Man Feng
- Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong Academy of Medical Sciences, 38 Wu Yingshan Road, Jinan 250031, China
| | - Ran Jiao
- Department of Operation Room, Ophthalmologic Hospital of Shandong Province, 372 Jing Si Road, Jinan 250021, China
| | - Dongyi Liu
- Department of Anesthesiology, The Second Hospital of Shandong University, 247 Bei Yuan Street, Jinan 250033, China
| | - Yanwu Jin
- Department of Anesthesiology, The Second Hospital of Shandong University, 247 Bei Yuan Street, Jinan 250033, China
| | - Xin Zhao
- Department of Anesthesiology, The Second Hospital of Shandong University, 247 Bei Yuan Street, Jinan 250033, China.
| | - Ruixue Xiao
- Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong Academy of Medical Sciences, 38 Wu Yingshan Road, Jinan 250031, China
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