Regulation of TGF-β1, 2, and 3 and IL-10 at systemic level in chronic liver disease

Abstract

Introduction and Objectives: Chronic liver disease (CLD) is considered an important health problem worldwide. The production of IL-10 regulated the hepatic inflammation. Whereas TGF-β plays a crucial role during the progression of CLD, promoting the dysregulated production of extracellular matrix in the liver. However, the role of TGF-β1, 2, and 3 and IL-10 in CLD is not completely understood. To evaluate the circulatory values of TGF-β1, 2, and 3 and IL-10 in hepatitis C virus (HCV), Non-alcoholic fatty liver disease (NAFLD) and alcoholic cirrhosis (OHCi) and control subjects (CT). Materials and Patients: A prospective, cross sectional, observational and multicentric study. HCV (n=33), NAFLD (n=33) and OHCi patients (n=22) and CT (n=26) were enrolled. The anthropometric variables, detailed clinical history and biochemical parameters were considered. TGF-β1, 2, and 3 and IL-10 (pg/mL) were evaluated using multiple suspension arrays. Kruskal-Wallis and Mann-Whitney U test were used for the statistical analysis. The study has the approval of the Research and Ethics Commissions with code FM/DI/135/2017 and the Research Ethics Committee of the Hospital General de México Dr. Eduardo Liceaga with code DI/16/107/03/031 as well the consent informed of the patients. Results: The age of CT group was estimated at 33 yrs., while the average of the different hepatopathies was 47 yrs. Male predominance was marked in OHCi and CT, but in NAFLD the distribution of women was similar. Multiple comparison analysis revealed that serum levels of TGF-β1, 2, and 3 did not present statistical differences in each CLD group. Nevertheless, TGF-β2 isoform showed significant difference in NAFLD and OHCi vs. CT (pNAFLD>HCV showing correlation with the increment of the ratio of 4.4, 2.7, and 2.3 folds compared to CT, respectively. Conclusions: Our data showed no differential changes of TGF-β1, 2, and 3 in accordance with CLD. The up regulation of TGF-β2 isoform could be related to different inflammatory responses in NAFLD and OHCi. On the other hand, IL-10 was upregulated in all the chronic conditions reflecting its role as pro-inflammatory mediator.