Candida albicans and Saccharomyces cerevisiae cell wall mannans produce fever in rats: role of nitric oxide and cytokines.

Mannan components of C. albicans (5 mg/kg, i.p.) and S. cerevisiae (2.5 mg/kg, i.p.) cell walls produced pyrogenic responses which were completely inhibited by indomethacin (5 mg/kg, s.c.) pretreatment in rats. A non-selective NOS inhibitor, L-NAME (10 mg/kg, s.c.), also inhibited the pyrogenic effectiveness of C. albicans mannan, whereas it was ineffective on the fever induced by S. cerevisiae mannan. A selective elevation in the serum TNF-alpha levels was observed at the initial phase of the fever due to S. cerevisiae mannan, whereas there was no significant change on the serum levels of TNF-alpha, IL-1beta and IFN-gamma during the latent period or at the initial phase of the fever induced by C. albicans mannan. Injections of N-linked and/or O-linked oligomannosides of the either mannan did not cause any significant change in the body temperature and serum cytokine levels. These data suggest that the mannan components of C. albicans and S. cerevisiae cell walls produce a prostaglandin-dependent fever in rats. The initial signal for fever seems to be different for each mannan. Data also indicate that integrity of the mannans is necessary for the pyrogenic response.