Abstract
Increased levels of IL-1 beta and IL-1 receptor antagonist (IL-1Ra) have been found in serum of patients with chronic liver diseases, although their expression 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 hepatitis (CAH) of varying degrees of severity. IL-1 beta and IL-1Ra mRNA expression was investigated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 31 patients with CAH of varying severity (classified as minimal/mild in 13 cases and moderate/severe activity in 18 cases) and in 12 control subjects. Quantitative evaluation of IL-1 beta and IL-1Ra corresponding bands was performed by densitometric image analysis, and expressed 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.), median 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 compared 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 significantly different IL-1 beta/IL-1Ra ratio emerged between controls, patients with moderate/severe CAH (2.22 +/- 0.48, median 2.76, range 0-6.12) and those with minimal/mild activity CAH (0.62 +/- 0.15, median 0.5, range 0-1.58, 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 comparison 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 between IL-1 beta and IL-1Ra, at the tissue level, may contribute to the pathogenesis and the activity of chronic active hepatitis C.