Human urine-derived inhibitors of interleukin 1

Human urine has been found to contain several different substances that are capable of inhibiting the in vitro effects of interleukin 1 (IL-1). The urine of febrile individuals contains elevated levels of a 30-40 kilodalton (kdal) glycoprotein that is a potent inhibitor of IL-1-induced proliferation of murine thymocytes. This inhibitor from febrile individuals also blocks antigen-induced activation of human peripheral blood lymphocytes in vitro but increases, rather than decreases IL-1-induced production of prostaglandin E2 by fibroblasts. Uromodulin, an 85-kdal glycoprotein derived from the urine of pregnant women, is also a potent inhibitor of IL-1-induced thymocyte proliferation and human lymphocyte activation. Differences in molecular weight, biologic activity, and antigenicity suggest that uromodulin and the febrile inhibitor are distinct entities. Urine of some individuals has also been found to contain large amounts of a third IL-1 inhibitor that is 20-25 kdal in size. Unlike the febrile inhibitor and uromodulin, this 25-kdal molecule has been found to be a potent inhibitor of IL-1-induced production of prostaglandin E2 by fibroblasts as well as of the proliferation of thymocytes. The biologic activities of these three inhibitors indicate that they may be part of an important physiologic system for the regulation of immunity and inflammation in humans.