Dysregulation of the cytokine network in the uterus of the diabetic rat

Insulin-dependent (type 1) diabetes is an auto-immune disorder that produce s secondary complications in numerous non-immunological systems. Changes in the synthesis and action pattern of several cytokines have been associated with the development of these alterations. Based on the clinical facts tha t the pregnant and non-pregnant functions of the reproductive system are al so disrupted by diabetes, our laboratory has decided to concentrate its res earch activities on the hypothesis that cytokines may be implicated in the uteropathy and embryopathy associated with the metabolic disorder. This rev iew article summarizes our major findings concerning the synthesis of TNF-a lpha and IL-1 beta in the uterus of diabetic rats, and in cultures of roden t uterine cells upon their exposure to high concentrations of glucose. The paper also reviews evidence that both the peri-implanting embryo and the ep ithelial cell layer lining the uterine lumen are targets for the deleteriou s influence of excess TNF-alpha. If confirmed in the uterus of diabetic pat ients, these observations may explain how cytokines contribute to the dysre gulation of crucial reproductive events like menstruation and embryo implan tation in humans.