EFFECTS OF ANTIPYRETICS ON MORTALITY DUE TO INFLUENZA-B VIRUS IN A MOUSE MODEL OF REYES-SYNDROME

Objectives: To determine the effects of acetylsalicylic acid (ASA) and acetaminophen on mortality due to influenza B infection in neonatal a nd weanling mice, as well as any synergistic, antagonistic or indiffer ent effects of the combined antipyretic and virus on mortality in mice pretreated with low doses of an industrial surfactant, Toximul MP8, w hich has been shown to reproduce many of the features of Reye's syndro me. In vitro studies were done to determine whether ASA or acetaminoph en altered the normal, interferon-mediated antiviral responses of mamm alian cells. The involvement of ASA or other commonly used xenobiotics in the induction of Reye's syndrome following virus illness has not b een resolved; to do so, and to elucidate the underlying metabolic mech anism, requires these studies in an animal model. Design: Prospective animal study. Animals: Newborn (945) and weanling (840) Swiss white mi ce, divided into 12 subgroups. Interventions: Some groups received Tox imul MP8 before inoculation with a dose of mouse-adapted human influen za B that produces 30% mortality (LD30); after infection, each subgrou p received either placebo, ASA or acetaminophen. Mortality counts were taken daily. The in vitro effects of the antipyretics on interferon r esponse were determined using standard virology techniques. Outcome me asure: Mortality, analyzed by survival curves (log rank test) or cumul ative daily mortality (chi(2) analysis). Plaque-reducing dose (PRD50) was used to determine the outcome of the in vitro analyses. Results: I n neonatal mice, only subgroups given combined treatment with acetamin ophen and Toximul MP8 had a statistically significant higher mortality rate than with the mice given influenza B alone. In weanling mice, it appeared that ASA shortened the time until death; however, this diffe rence was not statistically significant. In vitro studies demonstrated that both ASA and acetaminophen decreased the interferon-induced anti viral responses of cultured mammalian cells. Conclusion: Antipyretics have the potential to exacerbate the consequences of a viral infection , although the specific effects are subtle and appear to be age-relate d.