Inflammatory islet damage mediated by cytokines and oxygen radicals may limit the success of clinical islet transplantation for treatment of insulin- dependent diabetes mellitus. In this study, we investigated whether drugs such as currently used in islet-transplanted patients inhibit the release of IL-1β, TNFα, and superoxide from mononuclear blood cells in vitro. Methylprednisolone (10 μg/ml) inhibited the release of IL-1β and TNFα, but had no effect on superoxide generation. Both pentoxifylline (66 μg/ml) and cyclosporin A (300 ng/ml) slightly inhibited TNFα release without affecting IL-1β or superoxide generation. Nicotinamide (0.25 mM) did not interfere with the generation TNFα or superoxide and only slightly inhibited IL-1β production. A combination of methylprednisolone, pentoxifylline, cyclosporin A, and nicotinamide (concentrations for each substance as described above) inhibited TNFα generation by 74±6% (mean value±SEM, mononuclear blood cells from seven diabetic patients) without affecting IL-1β or superoxide generation. These data show that standard immunosuppressive therapy in islet transplanted patients may partially inhibit cytokine release but does not affect the generation of potentially islet-toxic superoxide from mononuclear cells.
- Immunosuppressive drugs
- Monocyte activation