Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum of activity against DNA and RNA viruses. It has been previously shown to attenuate the course of fulminant hepatitis in mice produced by murine hepatitis virus strain 3. We therefore studied the effects of ribavirin on murine hepatitis virus strain 3 replication, macrophage production of proinflammatory mediators including TNF, IL-1, and the procoagulant activity (PCA), fgl2 prothrombinase; and Th1/Th2 cytokine production. Although ribavirin had inhibitory effects on viral replication (<1 log), even at high concentrations complete eradication of the virus was not seen. In contrast, at physiologic concentrations (up to 500 μg/ml), ribavirin markedly reduced viral-induced parameters of macrophage activation. With ribavirin treatment, the concentrations of PCA, TNF-α and IL-1β all decreased to basal concentrations: PCA from 941 ± 80 to 34 ± 11 mU/106 cells; TNF-α from 10.73 ± 2.15 to 2.74 ± 0.93 ng/ml; and IL-1β from 155.91 ± 22.62 to 5.74 ± 0.70 pg/ml. The inhibitory effects of ribavirin were at the level of gene transcription as evidenced by Northern analysis. Both in vitro and in vivo, ribavirin inhibited the production of IL-4 by Th2 cells, whereas it did not diminish the production of IFN-γ in Th1 cells. In contrast, ribavirin had no inhibitory effect on TNF-α and IL-1β production in LPS-stimulated macrophages. These results suggest that the beneficial effects of ribavirin are mediated by inhibition of induction of macrophage proinflammatory cytokines and Th2 cytokines while preserving Th1 cytokines.
CITATION STYLE
Ning, Q., Brown, D., Parodo, J., Cattral, M., Gorczynski, R., Cole, E., … Levy, G. (1998). Ribavirin Inhibits Viral-Induced Macrophage Production of TNF, IL-1, the Procoagulant fgl2 Prothrombinase and Preserves Th1 Cytokine Production But Inhibits Th2 Cytokine Response. The Journal of Immunology, 160(7), 3487–3493. https://doi.org/10.4049/jimmunol.160.7.3487
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