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©2014 Baishideng Publishing Group Inc. All rights reserved.
Cytokine production in patients with cirrhosis and TLR4 polymorphisms
Juan Camilo Nieto, Elisabet Sánchez, Eva Román, Silvia Vidal, Laia Oliva, Carlos Guarner-Argente, Maria Poca, Xavier Torras, Cándido Juárez, Carlos Guarner, German Soriano
Juan Camilo Nieto, Silvia Vidal, Laia Oliva, Cándido Juárez, Department of Immunology, Institut de Recerca-IIB Sant Pau, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain
Elisabet Sánchez, Eva Román, Carlos Guarner-Argente, Maria Poca, Xavier Torras, Carlos Guarner, German Soriano, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
Elisabet Sánchez, Carlos Guarner, German Soriano, Department of Gastroenterology, Instituto de Salud Carlos III Institut de Recerca-IIB Sant Pau, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain
Elisabet Sánchez, Carlos Guarner, German Soriano, Department of Gastroenterology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 08025 Barcelona, Spain
Eva Román, Xavier Torras, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 08025 Barcelona, Spain
Eva Román, Department of Gastroenterology, Escola Universitària d’Infermeria Sant Pau, 08025 Barcelona, Spain
Eva Román, Department of Gastroenterology, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain
Author contributions: Nieto JC and Vidal S performed research, designed the experiments and analyzed data; Sánchez E, Oliva L and Román E contributed to acquisition and analysis of data; Guarner-Argente C, Poca M, Torras X and Guarner C contributed to acquisition of data; Juárez C contributed to analysis of data; Soriano G designed the experiments, contributed to the analysis and acquisition of data, and wrote the manuscript.
Supported by Health research fund “Fondo de Investigaciones Sanitarias” (to SV); Catalan Ministry of Health Stabilization Program; and Institute of Health Carlos III, Ministry of Science and Innovation, Grant No. PI09/00357, Madrid, Spain
Correspondence to: Silvia Vidal, PhD, Department of Immunology, Institut de Recerca-IIB Sant Pau, Universitat Autònoma de Barcelona, Avda. Antoni M.Claret, 167 (pavello 17), 08025 Barcelona, Spain. svidal@santpau.cat
Telephone: +34-93-5537544 Fax: +34-93-5537598
Received: February 13, 2014
Revised: April 22, 2014
Accepted: June 26, 2014
Published online: December 14, 2014
AIM: To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms.
METHODS: The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms, and 10 wild-type patients matched for age, sex and degree of liver failure. TLR4 polymorphisms were determined by sequence-based genotyping. Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation.
RESULTS: Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients (78% vs 20%, P = 0.02). Spontaneous production of interleukin (IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients [IL-6: 888.7 (172.0-2119.3) pg/mL vs 5540.4 (1159.2-26053.9) pg/mL, P < 0.001; IL-10: 28.7 (6.5-177.1) pg/mL vs 117.8 (6.5-318.1) pg/mL, P = 0.02]. However, the production of tumor necrosis factor-α, IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups.
CONCLUSION: TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients, suggesting that they play a role in the development of cirrhosis complications.
Core tip: The relationship between toll-like receptors (TLR) polymorphisms and the immune response is the focus of intensive research in chronic inflammatory conditions. This is the first study demonstrating that the presence of certain TLR4 polymorphisms is associated with a characteristic pattern of cytokine production. These polymorphisms could have a relevant role in the development of complications in patients with cirrhosis.
