Evidence for the Involvement of Sulfidopeptide Leukotrienes in the Pathogenesis of Pichinde Virus Infection in Strain 13 Guinea Pigs

摘要

Strain 13 guinea pigs inoculated subcutaneously with Pichinde virus developed fever, lost body weight, decreased water and food consumption, and died at 14 + or - 0.6 days. After FPL-55712, a leukotriene D4 antagonist, was administered beginning on PID (post-inoculation day) 3 for 18 days, the magnitude of body weight loss decreased and food intake increased, despite a persistent fever. The treated guinea pigs also survived significantly longer than infected animals receiving placebo injection (21 vs 14 days). Using guinea pig ileum bioassay and radioimmunoassay, we detected significant levels of plasma leukotrienes in Pichinde virus-infected guinea pigs on PID 11 and possibly PID 14. These findings strongly suggest that leukotrienes play a role in the pathogenesis of arenavirus infection and may account in part for the observed cardiac depression, pulmonary edema, and eventual death.