Interleukin-1 receptor antagonist plasma concentration is specifically increased by alpha-2A-interferon treatment

Background/Aims: The mechanisms of action of recombinant interferon-α (rIFNα) treatment in chronic hepatitis C is not fully understood, and may include modulation of the immune system as well as a direct antiviral effect. We have therefore evaluated the plasma concentrations of pro- and anti-inflammatory cytokines in patients with chronic hepatitis C before and during treatment with rIFNα. Methods: Twenty-three patients were studied. Plasma concentrations of IL-1β, IL-6, TNF, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptors (sTNFRs) type I and type II were determined twice before rIFNα treatment (on day −11 and day 1), and on days 11, 32 and 120 of treatment. Results: IL-1β, IL-6 and TNF plasma concentrations were rarely increased before treatment (in one, six and seven patients, respectively), and usually declined during treatment. sTNFRs I and II plasma concentrations were not increased either before or during treatment. This was not the case for IL-1RA. In untreated patients, the plasma concentration of IL-1RA was higher than normal in 16 out of 23 patients. When rIFNα treatment was initiated, there was a constant and dramatic increase in IL-1RA levels, which reached 8 times the upper limit of the normal range (p<0.001 as compared to pretreatment values). This increase was sustained up to day 120. Conclusions: These results indicate that induction of an anti-inflammatory status through modulation of the IL-1/IL-1RA balance may be a key mechanism of action of rINFα treatment in chronic hepatitis C.