Physiological significance of the interleukin 1 receptor accessory protein.
Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal-transducing component of the IL-1 receptor type I. The recent availability of IL-1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP. Animals were injected intraperitoneally with rat recombinant IL-1beta (200 ng/mouse), lipopolysaccharide (LPS, 5 microg/mouse), or subjected to 1-hour restraint stress. Neuroendocrine and immune parameters were measured 2 h after IL-1 or LPS injection or just after restraint. In wild-type controls, IL-1 and LPS activated the hypothalamic-pituitary-adrenal axis and increased plasma IL-6. In KO mice, the plasma levels of corticosterone and IL-6 increased after LPS, but not after rat recombinant IL-1beta. The LPS-induced depression of the lymphoproliferation was similar in wild-type and KO mice. Finally, the 1-hour restraint was able to increase the plasma levels of corticosterone in KO mice. These results show that IL-1RAcP is essential for physiological activities of peripheral IL-1, as it was previously demonstrated for those of brain IL-1. However, using IL-1RAcP KO mice, we were unable to demonstrate a specific role of endogenous IL-1 during LPS-induced inflammation. Moreover, stress-induced activation of the hypothalamic-pituitary-adrenal axis may occur in the absence of the IL-1-transducing receptor, IL-1RAcP.
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Laboratoire de Neurocytochimie Fonctionnelle, Université de Bordeaux I, Talence, France.
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology; D053577:Interleukin-1 Receptor Accessory Protein; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012149:Restraint, Physical; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology
C507765:IL1RAP protein, human; C507767:Il1rap protein, mouse; C507766:Il1rap protein, rat; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011506:Proteins; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D003208:Concanavalin A; D003345:Corticosterone