Immunomodulatory Effects of Aureobasidium pullulans SM-2001 Exopolymers on Cyclophosphamide-Treated Mice

The immunomodulatory effects of Aureobasidium pullulans SM-2001 exopolymers containing beta-1,3/1,6-glucan were evaluated in cyclophosphamide (CPA)-treated mice. To induce immunosuppression, 150 and 110 mg/kg of CPA were intraperitoneally injected 3 days and I day, respectively, before beginning administration of the test material. Exopolymers were delivered subcutaneously or orally, four times, in a volume of 10 ml/kg at 12-h intervals beginning 24 h after the second CPA treatment. Changes in thymus and spleen weights, splenic amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-10, and numbers of CD3+, CD4+, CD8+, and TNF-alpha+ thymus and spleen cells were monitored in CPA-treated mice. As a result of CPA treatment, dramatic decreases in the number of CD3+, CD4+, CD8+, and TNF-alpha+ cells were detected in the thymus and spleen, along with decreases in thymus and spleen weights. In addition, splenic TNF-alpha, IL-1 beta, and IL-10 contents were also decreased on observation with flow cytometry. However, oral and subcutaneous treatments with exopolymers effectively reduced the immunosuppressive changes induced by CPA. Therefore, it is concluded that exopolymers of A. pullulans SM-2001 can effectively prevent immunosuppression through, at least partially, the recruitment of T cells and TNF-alpha+ cells or enhancement of their activity, and can provide an effective component of prevention or treatment regimens for immunosuppression related to cancer, sepsis, and high-dose chemotherapy or radiotherapy.