항 바이러스제의 면역변조 효과

Abstract

In order to investigate the immunomodulatory effects of antivirals, we have studied the effects of ribavirin (RV), acyclovir (ACV), and isopurinosine (IP) on the immune responses of ICR mouse and on the proliferation and cytokine gene expression of human peripheral blood mononuclear cell (PBMC). Humoral and cell-mediated immune responses were investigated using ICR mice either immunized with sheep red blood cells (SRBC) or sensitized with dinitrofluorobenzene (DNFB). RV suppressed anti-SRBC antibody response, delayed-type hypersensitivity to SRBC as well as contact hypersensitivity to DNFB, whereas ACV and IP did not exhibit any immunomodulatory effects. T cell response was evaluated by the phytohemagglutinin (PHA)-stimulated PBMC proliferation assay. In this assay system, RV and ACV exhibited proliferation inhibition effects in a dose-dependent fashion. However, IP did not show any effect at low-dose ranges or exhibited marginal stimulatory effect at high-dose ranges of IP treatment. Immunomodulatory effects of these antiviral drugs were further investigated using the cytokine gene expression as the indicators. IP and ACV did not show any modulator effects on the expression of interleukin (IL)-2, IL-3, IL-4, IL-6, tumor necrosis factor, migration inhibitory factor and granulocyte macrophage-colony stimulating factor (GM-CSF) genes of PBMC which have been cultured in the presence or absence of PHA and phorbol myristate acetate (PMA). However, RV suppressed significantly the gene expression of IL-2, IL-3 and GM- CSF in the mitogen-stimulated PBMC. In conclusion, the observed suppressive effects of RV on immune responses in vivo, seem to be due to suppression of IL-2, IL-3 and GM-CSF gene expression and proliferation of PBMC, and IP and ACV seem to have unremarkable modulatory effects on immune system. Key Words: Antivirals, Immune response, Cytokine.