Nicotinamide inhibits enhanced in vitro production of interleukin-12 and tumour necrosis factor-alpha in peripheral whole blood of people at high risk of developing Type 1 diabetes and people with newly diagnosed Type 1 diabetes

Macrophages and T lymphocytes are the first cells to appear in pancreatic i slets in the development of autoimmune diabetes. It has been suggested that cytokines released by monocytes/macrophages, including interleukin-1 beta (IL-1 beta), interleukin-12 (IL-12) and tumour necrosis factor-alpha (TNF-a lpha) could have an initial role in islet B-cell damage. The aim of the pre sent study was to estimate the effect of human insulin and nicotinamide on the levels of monocyte/macrophage derived cytokines in the peripheral brood of humans at risk of Type 1 diabetes, and in patients with newly diagnosed Type 1 diabetes compared to healthy control subjects. The study was carrie d out on three groups of subjects: 20 first degree relatives of people with Type 1 diabetes (with two or more antibodies against pancreatic B-cell ant igens); 22 patients with recent onset of Type 1 diabetes (duration of the d isease 3-6 months); and 25 age-and sex-matched healthy subjects. Cytokine l evels (IL-I beta, IL-12, and TNF-alpha in the supernatants of whole blood c ultures incubated with PHA alone (10 mu g/ml), or PHA + human insulin (50 m u g/ml), or PHA + nicotinamide (100 mu mol/1) were quantified by ELISA. In the cultures with nicotinamide the concentration of IL-12 and TNF-alpha was significantly lower in the prediabetic group, diabetic patients, and the h ealthy controls than in the cultures with PHA only or with PHA + insulin. T here were no significant differences in IL-I beta production in the culture s after incubation with the different stimuli in the studied groups and hea lthy controls. No significant influence of human insulin on macrophage/mono cyte cytokines secretion in in vitro cultures of the peripheral blood was f ound. This suggests that nicotinamide could influence monocyte/macrophage f unction in peripheral blood by inhibiting production of IL-12 and TNF-alpha . (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.