Highest frequencies of interleukin-22-producing T helper cells in alcoholic hepatitis patients with a favourable short-term course.

Abstract

BACKGROUND: Alcoholic hepatitis (AH) has a severe prognosis due to hepatic inflammatory injury. The cytokine interleukin-22 (IL-22) is reported to exert anti-apoptotic and proliferative effects, but IL-22 has not been studied during the course of AH. IL-22 is mainly produced by CD4(+) (helper) T cells, including Th17 cells. In addition, Th17 cells produce the proinflammatory cytokine IL-17A, which has been implicated in AH. AIMS: We aimed to study the levels of circulating IL-22- and IL-17A-producing T helper cells and plasma cytokines in patients with AH and to examine the observations in relation to the short-term disease course. METHODS: We collected blood samples from 21 consecutive patients with severe AH on days 0, 14 and 30 after diagnosis, and included 10 stable alcoholic cirrhosis patients and 10 healthy subjects as controls. Analyses were performed using flow cytometry and ELISA. RESULTS: We found higher frequencies of IL-22-producing T helper cells in AH patients (median 1.7%) than in cirrhosis patients (1.0%, p = 0.03) and healthy controls (1.0%, p = 0.01), and a 1.5-fold increase in the plasma concentration of IL-17A in AH compared with healthy controls (p<0.01). Those patients who markedly improved their Glasgow Alcoholic Hepatitis Score demonstrated a 2-fold higher frequency of IL-22-producing T helper cells at baseline and during follow-up than patients whose condition deteriorated (p = 0.04). CONCLUSIONS: The frequency of IL-22-producing T helper cells was increased in AH patients and most so in those whose condition seemed to improve. T cell differentiation toward an IL-22-producing phenotype may thus be favourable in AH.