Modulation by biologic response modifiers of hepatitis C virus antigen-independent cytokine secretion in blood mononuclear cells.
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)gamma and interleukin (IL)-2] and Th2 (IL-4 and IL-10) phenotype, and the pro-inflammatory cytokines tumour necrosis factor alphaIL-1beta 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-beta 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-beta 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.
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018936:Hepatitis C Antigens; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007167:Immunotherapy; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism