614 SERUM GROWTH FACTORS AND APOPTOSIS MARKERS REFLECT INFLAMMATORY ACTIVITY IN CHRONIC HEPATITIS C

R-848 (TLR7/8L), c. serum from a patient chronically infected by HBV (as control), with high viraemia levels (−9 log10), d. serum from a patient chronically infected by HCV, with high viraemia levels (−7 log10), e. supernatant from 2215 hepatocytes (HBV progeny), f. various concentrations of ribavirin. Pulsing with all these stimuli took place either with or without the presence of CD40L-expressing cells as additional pDC activation stimulus. The aim was to explore the effect of the stimuli used, to the pDC Th1skewing capacity and type I IFN production (i.e. secretion of IFN-a, IL-6 and IL-12p40, in cell-culture supernatants, measured with commercially available ELISA kits) and to compare the effect of known TLR ligands (CpG ODN and R-848) to the effect of HCV and also the effect of a component of the currently established antiviral treatment (Ribavirin). Results: Our data demonstrate: a. stimulation of IL-6 production by CpG ODN and HBV serum/2215 S/N at comparable levels, stimulation of IL-6 production by R-848 at levels 3−4 times higher than the ones elicited by HCV serum, b. IL-12p40 production stimulation by R-848 at levels 3−4 times higher than the ones observed after incubation with HCV serum and also very high levels of IL-12p40 after stimulation with Ribavirin, c. IFNa production stimulated by CpG ODN and R-848 at levels comparable to the ones observed with HBV and HCV serum pulsing, respectively. Conclusions: It appears that: (a) the Th-1 skewing capacity of pDC is partially affected by HCV infection, (b) Ribavirin possibly exerts an immunomodulatory role by triggering IL-12 production (Th1 skewing).