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, ip) and S. cerevisiae (2.5 mg/kg , ip) cell walls produced pyrogenic responses which were completely inhibit ed by indomethacin (5 mg/kg, sc) pretreatment in rats. A non-selective NOS inhibitor, L-NAME (10 mg/kg, sc), also inhibited the pyrogenic effectivenes s 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-1 beta and IFN-gamma during the latent period or at the initial phase of the fever induced by C. albicans mannan, Injections of N-linlied and/or O- linked oligomannosides of the either mannan did not cause any significant c hange in the body temperature and serum cytokine levels. These data suggest that the mannan components of C. albicans and S. cerevisiae cell walls pro duce 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. (C) 2000 Elsevier Sci ence Inc. All rights reserved.