Abstract

Ribavirin (1-beta-D-ribofuranosyl-1,2-4-triazole-3-carboxamide) is a promising antiviral agent as well as a structural analog of guanosine. Although at different concentrations it has been reported to induce either immunosuppression or immune stimulation, its effects upon immediate hypersensitivity reactions are largely unknown. Because purine metabolism appears to be important in mast cell secretion, the effects of ribavirin on mouse bone marrow-derived mast cell functions were investigated. When ribavirin was added to mast cells at the time of stimulation with A23187 or specific antigen, no effect on the release of beta-hexosaminidase, a preformed mediator, was evident. However, mast cells cultured in 1 to 20 microM ribavirin for 1 to 7 days exhibited dose- and time-dependent inhibitions of stimulated beta-hexosaminidase and leukotriene C4 releases without altering mast cell mediator content. This inhibition occurred even when ribavirin had no effect on cell growth. A concomitant decrease in antigen-challenged mast cell intracellular Ca concentration was also observed after ribavirin treatment. Chronic ribavirin exposure in vitro inhibits mast cell secretory processes stimulated by both immunoglobulin E- and nonimmunoglobulin E-related signals. Its precise mechanism of action and any potential efficacy as an antiallergic agent remain to be elucidated.