Immunotherapeutic effects of pentoxifylline in type 1 diabetic mice and its role in the response of T-helper lymphocytes

Objective(s):Pentoxifylline is an immunomodulatory and anti-inflammatory agent and is used in vascular disorders. It has been shown that pentoxifylline inhibits proinflammatory [d1] cytokines production. The purpose of this study was to investigate the therapeutic effects of pentoxifylline on the treatment of autoimmune diabetes in mice. Materials and Methods: Diabetes was induced by multiple low dose of streptozotocin (MLDS) injection (40 mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with pentoxifylline (100 mg/kg/day IP) for 21 days. Blood glucose levels and plasma levels of insulin were measured. Splenocytes were tested for proliferation by MTT test and cytokine production by ELISA. Results: Pentoxifylline treatment prevented hyperglycemia and increased plasma insulin levels in the diabetic mice. Aside from reducing lymphocyte proliferation, pentoxifylline significantly inhibited the production of proinflammatory interleukin 17 (IL-17) as well as interferon gamma (IFN-γ), while increased anti-inflammatory cytokine IL-10 as compared with those in MLDS group (diabetic control group). Conclusion: These findings indicate that pentoxifylline may have therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of MLDS-induced type 1 diabetes in mice.