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

Abstract

Objectives: Pentoxifylline is an immunomodulatory and anti-inflammatory agent and is used in vascular disorders. It has been shown that pentoxifylline inhibits proinflammatory 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.

Keywords: Cytokine; Pentoxifylline; Type 1 diabetes mellitus.

Figure 1

Effect of pentoxifylline treatment on blood glucose levels (* P<0.05)

Figure 2

Effect of pentoxifylline treatment on plasma levels of insulin (* P<0.05)

Figure 3

Effect of pentoxifylline on productions of IFN γ IL-10 and IL-17 of diabetic murine splenocytes induced by Con A ex vivo (* P<0.05 versus diabetic control group)

Figure 4

Effects of pentoxifylline on the proliferation of splenic lymphocytes induced by con A after 72 hr (*P<0.05)