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 didnot 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 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 GMCSF 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.
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