TYPE-I INTERLEUKIN-1 RECEPTORS IN THE MOUSE-BRAIN ENDOCRINE-IMMUNE AXIS LABELED WITH [I-125] RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST

lodine-125-labelled recombinant human interleukin-I (IL-1) receptor antagonist ([I-125)IL-1ra) was utilized to further determine the characteristics of IL-1 receptors in the brain-endocrine-immune axis. The binding of [I-125]IL-1ra in homogenates of mouse hippocampus, spleen and testis was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity (K(D), 20-30 pM). In competition studies, IL-1ra, recombinant human IL-1alpha, IL-1beta and a weak IL-1beta analog inhibited [I-125]IL-1ra binding to mouse tissues in parallel with their biological activities. In autoradiographic studies, [I-125]IL-1ra and [I-125]IL-1alpha binding showed comparable distribution patterns with highest densities of binding sites present in the dentate gyrus of the hippocampus, choroid plexus, anterior pituitary, marginal zones and red pulp regions of the spleen, epididymus and interstitial area of the testis. The binding characteristics and distribution of [I-125]IL-ara are comparable to those of previously characterized Type I IL-1 receptors. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to physiological and pharmacological stimuli.