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 islets in the development of autoimmune diabetes. It has been suggested that cytokines released by monocytes/macrophages, including interleukin-1beta (IL-1beta), 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 blood 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-1beta, IL-12, and TNF-alpha) in the supernatants of whole blood cultures incubated with PHA alone (10 microg/ml), or PHA + human insulin (50 microg/ml), or PHA + nicotinamide (100 micromol/l) 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-1beta 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.
Kretowski
A
A
Department of Endocrinology, Medical Academy Bialystok, Poland. akretows@amb.ac.bialystok.pl
Myśliwiec
J
J
Szelachowska
M
M
Kinalski
M
M
Kinalska
I
I
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005190:Family; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009536:Niacinamide / Q000494:pharmacology*; D011236:Prediabetic State / Q000097:blood / Q000276:immunology*; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001323:Autoantibodies; D007328:Insulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C024211:islet cell antibody; D018664:Interleukin-12; D009536:Niacinamide