A PROTECTIVE ROLE OF PLATELET-ACTIVATING-FACTOR IN MURINE CANDIDIASIS

Platelet-activating factor (PAF) is a potent phospholipid-derived modu lator of immunological and inflammatory processes, In this study, the role of exogenous and endogenous PAF in resistance to infection with C andida albicans was investigated, Administration of PAF following a le thal challenge of C. albicans significantly protected mice from death and reduced the number of organisms in the kidneys. Neutralization of endogenous PAF with the PAF antagonist BN50739 shortened the mean surv ival time and increased the number of C, albicans cells per kidney. Sh ortly after infection of mice (30 min), significant levels of PAF were detected in the serum, PAF-induced protection appears to be mediated through the actions of tumor necrosis factor alpha (TNF-alpha), since pretreatment with anti-TNF-alpha before each injection of PAF abrogate d the majority of PAF-induced enhanced resistance. Administration of P AF in vivo elevated serum TNF-alpha levels and TNF-alpha mRNA expressi on in the kidney. Production of TNF-alpha was markedly diminished by p retreatment with the PAF antagonist BN50739 prior to infection with C. albicans. We conclude that PAF, which is produced during infection wi th C. albicans, plays an important role in determining the level of re sistance to this infectious microorganism, This effect of PAF appears to be mediated, at least in part, through the induction of TNF-alpha.