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 macroph ages/monocytes as well as cytotoxic T cells are responsible for pancreatic B-cell destruction in animal models of autoimmune diabetes and presumably i n insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the pres ent study was to evaluate the production of interleukin (IL)-13-a Th-2 cell s derived anti-inflammatory cytokine, by peripheral blood of newly diagnose d 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 o nset 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 direc ted against pancreatic B-cell antigens) (n = 20) or a low (with DQB1*0602 a llele) risk of type 1 diabetes development (n = 10) and a control age match ed group of healthy volunteers (n = 18). IL-13 concentrations in supernatan t of 72 h cultures of peripheral blood after incubation with phytohemagglut inin (PHA) or PHA+ insulin were quantified by enzyme-linked immunosorbent a ssay (ELISA). The levels of IL-13 in the supernatants were significantly lo wer 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 ha ve 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 t he IL-13 alterations could play an important role in the pathogenesis of ty pe 1 diabetes. We would speculate that IL-13 as an anti-inflammatory cytoki ne and a mediator of the Th-2 pathway could be the potential therapeutic ap proach in the prevention of type 1 diabetes.