Uromodulin, an Immunosuppressive Protein Derived from Pregnancy Urine, is an Inhibitor of Interleukin 1

• Published in: Proceedings of the National Academy of Sciences - PNAS 1986-12, Vol.83 (23), p.9119-9123
• Main Authors: Brown, Kathryn M., Muchmore, Andrew V., Rosenstreich, David L.
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antibodies; Antibodies, Monoclonal; Biological and medical sciences; Female; Fever - urine; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gels; Humans; Immunobiology; Immunologic Techniques; Immunology; Interleukin-1 - antagonists & inhibitors; Interleukins; Lymphocyte Activation; Lymphocytes; Lymphokines, interleukins ( function, expression); Mice; Molecular Weight; Mucoproteins; Phosphates; Pregnancy; Pregnancy - urine; Pregnancy Proteins - immunology; Pregnancy Proteins - pharmacology; Regulatory factors and their cellular receptors; Thymocytes; Urine; Uromodulin
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.23.9119

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.