Uromodulin, an immunosuppressive protein derived from pregnancy urine, is an inhibitor of interleukin 1.

Uromodulin, an 85-kDa glycoprotein isolated from pregnancy urine, has been shown to inhibit antigen-induced proliferation of human lymphocytes in vitro. The present investigation was undertaken to determine its mechanism of action. Uromodulin was found to be a potent inhibitor of interleukin 1 (IL-1)-induced thymocyte proliferation. Uromodulin was compared to a previously described 30- to 35-kDa IL-1 inhibitor isolated from urine of febrile patients (febrile inhibitor). Uromodulin and the febrile inhibitor blocked the effects of both human IL-1 and recombinant murine IL-1, but the activity of uromodulin was greater than that of the only partially purified febrile inhibitor preparation. However, in contrast to the febrile inhibitor, uromodulin markedly enhanced interleukin 2-induced thymocyte proliferation. Antigenic analysis of the two preparations by ELISA and immunoblot analysis demonstrated that the febrile inhibitor did not cross-react with uromodulin using monoclonal or polyclonal antisera. These findings indicate that uromodulin is a potent IL-1 inhibitor that is probably distinct from the IL-1 inhibitor derived from the urine of febrile individuals. Whether this IL-1 inhibitory activity underlies its immunosuppressive activity on human lymphocytes remains to be established.