Modulation by biologic response modifiers of hepatitis C virus antigen-independent cytokine secretion in blood mononuclear cells

Abstract

The systemic hepatitis C virus (HCV) antigen-non-specific cytokine responses were investigated in cultures of peripheral blood mononuclear cells. Cytokines of the T helper (Th) 1 [interferon (IFN)γ and interleukin (IL)-2| and Th2 (IL-4 and IL-10) phenotype, and the pro-inflammatory cytokines tumour necrosis factor α, IL-1β and IL-6, were secreted by the cells activated by the HCV antigen-independent pathway. Furthermore, these cytokine responses were shifted towards a Th1 predominance by treatment with IFN-β and with IL-2, whereas cytokine responses were selectively amplified towards a combined Th1-Th2 profile by granulocyte-macrophage- but not by macrophage colony-stimulating factor. Moreover, pro-inflammatory cytokine production was significantly enhanced by IFN-β and augmented dose-dependently with GM-CSF and IL-2. Therefore, these immune mediators can promote unique - as well as overlapping - systemic cytokine responses that may be relevant for immunotherapeutic interventions to control HCV infection.