The Immune Responsiveness in Hepatitis C Virus Infected Patients: Effects of Interferon-Alfa / Ribavirin Combined Treatment on the Lymphocyte Response with Special Reference to B Cells

Previous data demonstrated that an elevated percentage of hepatitis C virus (HCV) infected patients are endotoxemic. Endotoxemic patients are poor responders to the interferon (IFN)- α / ribavirin (RIB) treatment and exhibit lower serum levels of IFN-γ and interleukin (IL)-10 than the responder counterpart. Here we provide evidence that in endotoxemic HCV+ patients absolute numbers of CD19+ cells (B cells) are higher than those observed in the non-endotoxemic counterpart at the end of the combined treatment. Moreover, anti lactoferrin (LF) antibodies are more elevated in non-responder HCV+ patients than in the responders. In turn, these autoantibodies may affect the antiviral activity of LF, on the one hand , and, on the other hand abrogate the LF binding to lipopolysaccharides (LPS). Such an interaction hampers the binding of LPS to LPS binding protein, thus inhibiting LPS fixation to CD14+ cells and, ultimately, leading to a decreased release of proinflammatory cytokines.