Glucan-induced modification of the increased susceptibility of cyclophosphamide-treated mice to Staphylococcus aureus infection

Summary Glucan, a 1–3-polyglucosidic component of the cell wall of Saccharomyces cerevisiae, was evaluated for its ability to modify experimentally induced S. aureus septicemia in an immunosuppressed mouse model. AKR/J mice were injected with glucan (0.45 mg), cyclophosphamide (0.6 mg), isovolumetric saline (0.5 ml), or glucan (0.45 mg) and cyclophosphamide (0.6 mg) on days –10, –7, –4 and –1 prior to intravenous challenge with 1.0×10⁹ S. aureus on day 0.In contrast to the significant (P<0.05) decrease in leukocytes observed in the cyclophosphamide-treated mice, the administration of glucan to cyclophosphamide-treated mice resulted in maintenance of the peripheral leukocyte counts. Furthermore, glucan, as a single pretreatment regimen, resulted in a median survival time of 12.5 days, as against only 7.5 days in the saline control group. A 1.4-day median survival was observed in mice pretreated with cyclophosphamide and subsequently challenged with S. aureus. However, when glucan and cyclophosphamide were administered together, a median survival time of 9.0 days was observed.Histopathologic examination revealed that glucan administration inhibited the renal necrosis observed in both normal and cyclophosphamide-treated mice following staphylococcal challenge. Glucan also produced a marked reduction of hepatic pathology in cyclophosphamide-treated mice following S. aureus challenge. These data denote that glucan administration is effective in altering morbidity and mortality due to systemic S. aureus disease in cyclophosphamide-treated mice.