In vitro interleukin-13 production by peripheral blood in patients with newly diagnosed insulin-dependent diabetes mellitus and their first degree relatives.
It is generally accepted that proinflammatory cytokines secreted by macrophages/monocytes as well as cytotoxic T cells are responsible for pancreatic B-cell destruction in animal models of autoimmune diabetes and presumably in insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to evaluate the production of interleukin (IL)-13-a Th2 cells derived anti-inflammatory cytokine, by peripheral blood of newly diagnosed IDDM patients and their first degree relatives with a low or high risk of IDDM development. The study was carried out in 20 patients with a recent onset of type 1 diabetes, their first degree relatives with high (with DRB1*03 and/or DRB1*04 HLA class II alleles and two or more autoantibodies directed against pancreatic B-cell antigens) (n = 20) or a low (with DQB1*0602 allele) risk of type 1 diabetes development (n = 10) and a control age matched group of healthy volunteers (n = 18). IL-13 concentrations in supernatant of 72 h cultures of peripheral blood after incubation with phytohemagglutinin (PHA) or PHA+ insulin were quantified by enzyme-linked immunosorbent assay (ELISA). The levels of IL-13 in the supernatants were significantly lower in at high risk of IDDM first degree relatives of diabetic patients (P < 0.02), higher in subjects with low genetic risk of diabetes type 1 (P < 0.02), and normal in IDDM patients in comparison to the control group. We have also observed that the adding of human insulin to the cultures resulted in a significant increase of in vitro IL-13 production in prediabetics, but not in the other studied groups. In conclusion our findings suggest that the IL-13 alterations could play an important role in the pathogenesis of type 1 diabetes. We would speculate that IL-13 as an anti-inflammatory cytokine and a mediator of the Th2 pathway could be the potential therapeutic approach in the prevention of type 1 diabetes.
Kretowski
A
A
Department of Endocrinology, Medical Academy of Bialystok, Poland.
Myśliwiec
J
J
Kinalska
I
I
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000097:blood* / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D018793:Interleukin-13; D010835:Phytohemagglutinins; D011994:Recombinant Proteins