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. So far, no receptor subtype-specific ligands have been described. Since both types of IL-1 receptors occur in the thermoregulatory areas it was unclear which IL-1 receptor type mediates fever. We report here that for a series of deletion mutants of human recombinant IL-1 beta (hrIL-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 beta > des-SND52-54 > des-QGE48-50 > des-I56). Thus, the results suggest that agonist occupancy of the type I IL-1 receptor is essential for IL-1 beta-mediated fever.
Malinowsky
D
D
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
Chai
Z
Z
Bristulf
J
J
Simoncsits
A
A
Bartfai
T
T
D000818:Animals; D005334:Fever / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D017353:Gene Deletion; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008024:Ligands; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D008024:Ligands; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins