Imbalance of IL-1 beta and IL-1 receptor antagonist mRNA in liver tissue from hepatitis C virus (HCV)-related chronic hepatitis

Increased levels of IL-1 beta and IL-1 receptor antagonist (IL-1Ra) have be en found in serum of patients with chronic liver diseases, although their e xpression in liver tissue has not been extensively investigated. The aim of this study was therefore to examine the relationship between IL-1 beta and IL-1Ra at tissue level in patients with HCV-related chronic active hepatit is (CAH) of varying degrees of severity. IL-1 beta and IL-1Ra mRNA expressi on was investigated by semiquantitative reverse transcription-polymerase ch ain reaction (RT-PCR) in 31 patients with CAH of varying severity (classifi ed as minimal/mild in 13 cases and moderate/severe activity in 18 cases) an d in 12 control subjects. Quantitative evaluation of IL-1 beta and IL-1Ra c orresponding bands was performed by densitometric image analysis, and expre ssed in arbitrary units. The 12 controls expressed a similar pattern with a mean IL-1 beta/IL-1Ra ratio of 1.03 (1.03 +/- 0.15 (mean +/- s.e.m.), medi an 0.92, range 0.71-1.45). Minimal/mild activity CAH showed a prevalence of IL-1Ra mRNA expression (1.14 +/- 0.64, median 0.43, range 0-8.75) when com pared with controls (0.27 +/- 0.04, median 0.23, range 0.11-0.45) and with moderate/severe activity CAH (0.20 +/- 0.04, median 0.12, range 0-0.67; P = 0.01). Since IL-1 beta expression was similar in the three groups, a signi ficantly different IL-1 beta/IL-1Ra ratio emerged between controls, patient s with moderate/severe CAH (2.22 +/- 0.48, median 2.76, range 0-6.12) and t hose with minimal/mild activity CAH (0.62 +/- 0.15, median 0.5, range 0-1.5 8, P = 0.005). Patients with higher grades of fibrosis showed a higher IL-1 beta/IL-1Ra ratio (2.49 +/- 0.56, median 2.15, range 0.35-6.12) in compari son with lower grade fibrosis (1.06 +/- 0.30, median 0.59, range 0.03-4.50) and control patients (P = 0.01). These results suggest that an imbalance b etween IL-1 beta and IL-1Ra, at the tissue level, may contribute to the pat hogenesis and the activity of chronic active hepatitis C.