Yeast (1 -> 3)-(1 -> 6)-beta-D-glucan alleviates immunosuppression in gemcitabine-treated mice

Abstract

Gemcitabine (2'-deoxy-2',2'-difluorocytidine, dFdC) is one of the most effective chemotherapy drugs commonly used for treatment of various tumors. Despite its significant anticancer effects, some adverse effects create obstacles to treatment. The main toxicity of gemcitabine is myelosuppression, which not only reduces patient quality of life, but also hinders further anticancer treatment. In this respect, immunotherapy can address these drawbacks because of its ability to enhance the patient's immune system. To improve immune system function, yeast-derived beta-glucans, which are well-known biologic response modifiers, were administered to gemcitabine-treated mice. The in vivo experiment revealed that orally administered yeast (1 -> 3)-(1 -> 6)-beta-glucan effectively alleviated myelosuppression associated with gemcitabine-induced pancytopenia. Moreover, analysis of myelopoiesis-related cytokine expression through real-time PCR demonstrated that beta-glucan treatment significantly upregulated hematopoietic responses in gemcitabine-treated mice. Furthermore, orally administered beta-glucan significantly induced the expression of IFN-gamma, and IL-2 in splenocytes of gemcitabinetreated mice. It also restored the cytotoxicity of splenocytes against YAC-1 in gemcitabine-treated mice and displayed a positive effect on gemcitabine-damaged bone marrow tissue. In conclusion, yeast beta-glucans have the potential to be used as adjuvants for alleviating chemotherapy-induced immunosuppression in patients. (C) 2019 Elsevier B.V. All rights reserved.