Action site of circulating interleukin-1 on the rabbit brain.
Interleukin-1 (IL-1) is now generally accepted as an endogenous pyrogenic mediator of fever induction. IL-1 induces fever by means of activation of arachidonate metabolism in the brain. However, whether circulating IL-1 enters the brain or not, further, the question of where is the action site of circulating IL-1 on the brain, have not been clearly demonstrated. In the present study, to investigate the site of action of circulating IL-1 on the brain, recombinant rabbit interleukin-1 beta (IL-1 beta) was labeled with colloidal gold, injected into the carotid artery of anesthetized rabbits and traced in the brain tissue by means of electron microscopy. Dose-dependent increase in colonic temperature was induced by intravenous injection of used IL-1 in rabbits, while heated IL-1 beta lost the pyrogenicity. Injection of solution of colloidal gold per se did not affect the colonic temperature of afebrile conscious rabbits. However, the IL-1/gold conjugates induced fever; IL-1 beta retained its pyrogenic potency even after labeling with gold. By electron microscopy, the IL-1/gold conjugates were observed on the surface and in the vesicle of endothelial cells of the capillary in the region of the anteroventral third ventricle. This implies that circulating IL-1 acts, as the initial step to induce fever, on the endothelium in that region.
Hashimoto
M
M
Department of Physiology, Yamanashi Medical College, Japan.
Ishikawa
Y
Y
Yokota
S
S
Goto
F
F
Bando
T
T
Sakakibara
Y
Y
Iriki
M
M
D000818:Animals; D001812:Blood-Brain Barrier; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D002196:Capillaries / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D002552:Cerebral Ventricles / Q000098:blood supply; D003102:Colloids; D003106:Colon; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005334:Fever / Q000139:chemically induced; D006046:Gold; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
D003102:Colloids; D007375:Interleukin-1; D011994:Recombinant Proteins; D006046:Gold