Nicotinamide inhibits enhanced in vitro production of interleukin-12 and tumour necrosis factor-α 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 islets 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-alpha) could have an initial role in islet B-cell damage. The aim of the present 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 carried 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 antigens); 22 patients with recent onset of Type 1 diabetes (duration of the disease 3-6 months); and 25 age-and sex-matched healthy subjects. Cytokine levels (IL-I beta, IL-12, and TNF-alpha in the supernatants of whole blood cultures incubated with PHA alone (10 mu g/ml), or PHA + human insulin (50 mu 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 healthy controls than in the cultures with PHA only or with PHA + insulin. There were no significant differences in IL-I beta production in the cultures after incubation with the different stimuli in the studied groups and healthy controls. No significant influence of human insulin on macrophage/monocyte cytokines secretion in in vitro cultures of the peripheral blood was found. This suggests that nicotinamide could influence monocyte/macrophage function in peripheral blood by inhibiting production of IL-12 and TNF-alpha. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.