Effects of the ribavirin-interferon alpha combination on cultured peripheral blood mononuclear cells from chronic Hepatitis C patients.

Cytokine 1998 Aug;10(8):635-644

Martin J, Navas S, Quiroga JA, Pardo M, Carreno V

Department of Hepatology, Fundacion Jimenez Diaz, Madrid, Spain.
The effects of ribavirin and interferon (IFN) alpha have been investigated on cultured peripheral blood mononuclear cells, obtained from 15 patients with chronic Hepatitis C virus (HCV) infection. At clinically relevant serum concentrations achieved during therapeutic administration, ribavirin did inhibit moderately the mitogen-stimulated mononuclear cell proliferation and growth of the CD4+ and CD8+ T cell subsets without apparent cytolysis. The ribavirin-IFN-alpha combination showed activity against HCV with disappearance of HCV RNA in 27% of cases, and a synergy in the inducibility of the intracellular enzyme 2′,5′-oligoadenylate synthetase. Such ribavirin concentrations induced modest increases in the T helper 1-like cytokine production by mononuclear cells. Higher ribavirin concentrations markedly inhibited IFN-gamma production, but augmented interleukins (IL) 2, 4, and 12 secretion. Conversely, IFN-alpha tended to suppress IL 2, 4 and 12, but enhanced IFN-gamma and IL-10 secretion. Thus, ribavirin and IFN-alpha appear to cause diverse effects on immunoregulatory cytokine secretion, and when combined, counteracted for production of IL-2 and IL-12, while upregulated mononuclear cell secretion of IFN-gamma and that of the anti-inflammatory cytokine IL-10. These findings suggest a non-cytolytic modulation of inflammatory responses induced by the drug combination, that may be relevant in the pathophysiology of chronic HCV infection.

PMID: 9722937, UI: 98390177