THE TYPE-I INTERLEUKIN-1 RECEPTOR MEDIATES FEVER IN THE RAT AS SHOWN BY INTERLEUKIN-1 RECEPTOR SUBTYPE-SELECTIVE LIGANDS

The interleukin-1 (IL-1) system possesses two distinct receptors (type I and type II) which, together with the accessory protein, mediate a multitude of responses to IL-1 alpha and IL-1 beta, including fever. S o far, no receptor subtype-specific ligands have been described. Since both types of IL-1 receptors occur in the thermoregulatory areas it w as unclear which IL-1 receptor type mediates fever. We report here tha t for a series of deletion mutants of human recombinant IL-1 beta (hrI L-1 beta), the affinity of these ligands for the type I IL-1 receptor correlates with their efficacy to evoke the fever response (hrIL-1 bet a > des-SND52-54 > des-QGE(48-50) > des-I-56). Thus, the results sugge st that agonist occupancy of the type I IL-1 receptor is essential for IL-1 beta-mediated fever.