Selective inhibition of functional lymphocyte subpopulations by ribavirin

Abstract

The present studies were designed to examine the effects of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a broad-spectrum antiviral agent, on the generation of murine antibody responses in vitro. Whereas primary and secondary sheep erythrocyte-specific, plaque-forming cell responses by normal murine spleen cells were enhanced by low concentrations of ribavirin (1 microgram per culture), they were strongly inhibited by higher concentrations of ribavirin (5 to 10 micrograms per culture). Both phenomena occurred with the greatest magnitude when spleen cells were exposed to ribavirin 48 to 72 h after culture initiation. Enhancement appeared to result from selective interference with suppressor T cells, since ribavirin failed to augment lipopolysaccharide-specific plaque-forming cell responses in T cell-depleted spleen cell cultures but inhibited concanavalin A-induced lymphocyte proliferation and suppressor T cell generation in cultures of normal spleen cells. The immunosuppressive properties of ribavirin were mediated by a direct antiproliferative effect and, at higher concentrations, a cytotoxic effect for B lymphocytes, since the drug inhibited plaque-forming cell responses in T cell-depleted spleen cell cultures, suppressed lipopolysaccharide-induced lymphocyte proliferation and reduced viable spleen cell recoveries.

Determining Ribavirin’s mechanism of action against Lassa virus infection

“…Similar observations have been made during influenza virus infection, where ribavirin improved survival rate and lung pathology without reducing viremia in the lungs 36 . The potential mechanisms leading to the observed cell protective effect remain unresolved, but possible explanations include ribavirin’s modulation of immunological and pathophysiological pathways 37 , 38 , thereby inhibiting macrophage activation and cytokine production 37 ; and the anti-proliferative effect on lymphocytes observed at high concentrations of ribavirin 39 . The discrepancy between ribavirin’s antiviral efficacy observed in vitro 7 and its main mechanism of action in vivo could be due to different factors, including the type of cells infected and the actual pharmacokinetics.…”

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

“…Also, in two separate cases, one in Thailand, and one in the United States, ribavirin was administered, again demonstrating a lack of efficacy [46,48]. It is hypothesized that this disappointing performance of ribavirin is due to its interference with the Th1/Th2 immune response, thus hindering production of effective antibodies that are essential for RABV clearance [49].…”

Role of Virus-Specific Immunoglobulin E Antibody Responses in Obstructive Airway Disease

“…In in vitro assays using nonreplicating agents, ribavirin has been shown to inhibit the development of antibody responses. 34 In a study of infants receiving either no therapy, a placebo, or ribavirin for bronchiolitis, it was demonstrated that both RSV-specific IgA and IgE antibody responses were inhibited in the ribavirin-treated group 35 (Table 5). In addition, purine nucleosides and nucleotides may modulate mast cell secretion, and it has been demonstrated that ribavirin inhibits the release of preformed granules similar to histamine as well as reducing synthesis of LTs from murine mast cells.…”