Effects of antipyretics on mortality due to influenza B virus in a mouse model of Reye's syndrome

Objectives: To determine the effects of acetylsalicylic acid (ASA) and acetaminophen on mortality due to influenza B infection in neonatal and weanling mice, as well as any synergistic, antagonistic or indifferent effects of the combined antipyretic and virus on mortality in mice pretreated with low doses of an industrial surfactant, Toximul MP8, which has been shown to reproduce many of the features of Reye's syndrome. In vitro studies were done to determine whether ASA or acetaminophen altered the normal, interferon-mediated antiviral responses of mammalian cells. The involvement of ASA or other commonly used xenobiotics in the induction of Reye's syndrome following virus illness has not been resolved; to do so, and to elucidate the underlying metabolic mechanism, requires these studies in an animal model. Design: Prospective animal study. Animals: Newborn (945) and weanling (840) Swiss white mice, divided into 12 subgroups. Interventions: Some groups received Toximul MP8 before inoculation with a dose of mouse-adapted human influenza B that produces 30% mortality (LD₃₀); after infection, each subgroup received either placebo, ASA or acetaminophen. Mortality counts were taken daily. The in vitro effects of the antipyretics on interferon response were determined using standard virology techniques. Outcome measure: Mortality, analyzed by survival curves (log rank test) or cumulative daily mortality (χ² analysis). Plaque-reducing dose (PRD₅₀) was used to determine the outcome of the in vitro analyses. Results: In neonatal mice, only subgroups given combined treatment with acetaminophen 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 difference was not statistically significant. In vitro studies demonstrated that both ASA and acetaminophen decreased the interferon-induced antiviral 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-related.