Interleukin-1 receptor antagonist attenuates cyclophosphamide-induced mucositis in a murine model

Cyclophosphamide is a cytotoxic chemotherapy drug that causes severe damages to hematopoietic and gastrointestinal systems. The aim of this study is to evaluate the protective effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on chemotherapy-induced mucositis (CIM) in a murine model of cyclophosphamide chemotherapy. In single chemotherapy models, equal numbers of gender-matched Balb/c mice were administered intraperitoneal injections of rhIL-1Ra at a dose of 1 mg/kg/day or vehicle for 5 continuous days, followed by single intraperitoneal injection of cyclophosphamide at doses of 100, 300, 400 or 550 mg/kg. In multiple cycles of chemotherapy models, mice were administered rhIL-1Ra or vehicle for 5 days, followed by cyclophosphamide injection at a dose of 300 mg/kg. The course has been repeated for 2 or 3 times with a 1-month break in between. In continuous chemotherapy models, mice were administered rhIL-1Ra or vehicle for 5 days, followed by cyclophosphamide injections at doses of 150 or 200 mg/kg/day for 3 days. Body weight and diarrhea were observed in each model. Intestinal morphology was observed in mice received 300 or 400 mg/kg cyclophosphamide chemotherapy. CIM was induced by cyclophosphamide in a dose-dependent manner. RhIL-1Ra attenuated CIM with reduced body weight loss, diarrhea, intestinal injuries and mortality after CY chemotherapy. The pretreatment with rhIL-1Ra effectively protected murine gastrointestinal system from clinically relevant cyclophosphamide regimens. The identification of these protective effects of rhIL-1Ra highlights clinical values of this protein for the prevention of CIM.