MESSENGER-RNA CYTOKINE PROFILE IN PERIPHERAL-BLOOD CELLS FROM CHRONICHEPATITIS-C VIRUS (HCV)-INFECTED PATIENTS - EFFECTS OF INTERFERON-ALPHA (IFN-ALPHA) TREATMENT

Natural immune responses, both cellular and humoral, are not capable o f terminating HCV infection in most patients. A role has been suggeste d for peripheral blood leucocytes (PBL) in viral persistence and clini cal implications, as these cells may serve as a viral reservoir and at the same time may be inadequate active participants in antiviral immu ne reactions. IFN-alpha administration, although only partially succes sful, is currently the main therapy available for chronic HCV patients . In addition to its antiviral effects, IFN-alpha regulates the functi on of cytokines, their receptors and other molecules of immune importa nce. The aim of this study was to determine cytokine mRNA expression i n PBL derived from chronic HCV patients prior to and at termination of IFN-alpha treatment. HCV RNA was still observed in sera of most patie nts (10 out of 14 treated patients) at termination of treatment. In pr etreated patients mRNA expression of Th2 (IL-4, IL-6 and IL-10) and Th 3 (transforming growth factor-beta (TGF-beta) was observed in only a l ow percentage of PBL samples from patients, similar to controls. IFN-a lpha treatment led to an elevation in the number of samples expressing these cytokines (significant for IL-4, IL-6, IL-10, tumour necrosis f actor-alpha (TNF-alpha) and TGF-beta), accompanied by reduction in liv er enzymes but in serum viral load in only approximate to 30% of patie nts. Expression of TNF-alpha and TNF-beta mRNA was observed in samples from patients but not controls, while no differences were observed fo r mRNA of classical Th1 cytokines (IL-2 and IFN-gamma) between patient s before or during treatment as well as controls. The cytokine mRNA pr ofile following IFN-alpha treatment points to an anti-inflammatory res ponse which does not appear to be involved in termination of the viral infection. The PBL cytokine profile observed in this study may explai n the failure of the immune system to eradicate HCV chronic infection and suggests that early treatment in the acute phase of disease with a gents that stimulate cytotoxic immune type 1 responses may lead to era dication of HCV infection.