Importance of Interleukin-1 and Interleukin-1 Receptor Antagonist in Short-Term Glucose Sensor Function in Vivo

Abstract

Background: The importance of the interleukin (IL)-1 cytokine family in inflammation and immunity is well established as a result of extensive in vitro and in vivo studies. In fact, much of our understanding of the in vivo importance of interleukin-1beta (IL-1B) is the result of research utilizing transgenic mice, such as overexpression or deficiencies of the naturally occurring inhibitor of IL-1 known as interleukin-1 receptor antagonist (IL-1RA). For the present studies, we utilized these transgenic mice to determine the role of IL-1B in glucose sensor function in vivo. Methods: To investigate the role of IL-1B in glucose sensor function in vivo, we compared glucose sensor function in transgenic mice that (1) overexpressed IL-1RA [B6.Cg-Tg(II1rn)1Dih/J] and (2) are deficient in IL-1RA (B6.129S- Il1rntm1Dih/J), with mice that have normal levels of IL-1RA (C57BL/6). Results: Our studies demonstrated that, during the first 7 days post-sensor implantation (PSI), mice deficient in IL-1RA had extensive inflammation and decreased sensor function when compared to normal or IL-1RA-overexpressing mice. Conclusion: These data directly support our hypothesis that the IL-1 family of cytokines and antagonists play a critical role in controlling tissue reactions and thereby sensor function in vivo during the first 7 days PSI.