Interleukin 1 receptor accessory protein (IL-1RAcP) is necessary for centrally mediated neuroendocrine and immune responses to IL-1beta.

Mice deficient for the IL-1RAcP gene (IL-1RAcP KO) were used to explore the role of IL-1RAcP in physiological functions of brain IL-1beta. Animals were injected i.c.v. with two different doses of recombinant human (rh) IL-1beta: a small one (750 pg) known to induce sickness behavior, and a larger one (50 ng), chosen to counteract the possible loss of affinity of IL-1beta on its receptor. Neuroendocrine and immune parameters were measured 2 h after IL-1 injection. The increase of plasma corticosterone induced by rhIL-1beta in wild-type (WT) mice was not observed in IL-1RAcP KO mice. Likewise, the depression of splenocyte proliferation occurred in WT but not in KO mice. Finally, in opposition to WT mice, plasma levels and brain cortical content of IL-6 in IL-1RAcP KO mice remained unchanged as compared to saline-injected controls. The results clearly demonstrate that IL-1RAcP is necessary for the induction of the main neuroendocrine and immune effects of central IL-1beta.