Increased in vitro interleukin-12 production by peripheral blood in high-risk IDDM first degree relatives.
Cytokines secreted by antigen presenting cells, lymphocytes T and pancreatic beta cells are considered as the major mediators in the pathogenesis of IDDM. It has been suggested that cytokines released by macrophages/monocytes could have an initial role in beta-cell damage. The aim of the present study was the estimation of in vitro production of macrophage-derived cytokines: IL-1 beta, TNF-alpha, IL-12 by peripheral blood in high risk IDDM first degree relatives, since it could reflect early events leading to the development of type 1 diabetes in humans. The study was performed in 25 high risk IDDM subjects and 21 age and sex-matched healthy controls. IL-1 beta, TNF-alpha and IL-12 concentrations in supernatants of whole blood cultures with PHA (10 micrograms/ml) were quantified by ELISA. In the ICA positive relatives of IDDM subjects levels of IL-12 were significantly higher as compared with the control group, both at 48 h (p < 0.02) and at 72 h (p < 0.05) of incubation and positively correlated with TNF-alpha and IL-1 beta (R = 0.46, p < 0.02 and R = 0.32, p < 0.05). We did not observe statistical differences in in vitro production of TNF-alpha and IL-1 beta between the study groups. In conclusion we suggest that our findings support the hypothesis, that IL-12 is involved in the pathogenesis of human IDDM. If the involvement of Th1 cells is confirmed in the destruction of islet beta-cells, it is possible that IL-12 antagonists will have a role in the future prevention of insulin dependent diabetes mellitus.
Szelachowska
M
M
Department of Endocrinology, Medical School Bialystok, Poland.
Kretowski
A
A
Kinalska
I
I
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001773:Blood Cells / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D009679:Nuclear Family; D010835:Phytohemagglutinins; D012016:Reference Values; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001323:Autoantibodies; D007375:Interleukin-1; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C024211:islet cell antibody; D018664:Interleukin-12