Interleukin-1 receptor antagonist: effectiveness against interleukin-1 fever.
Conscious cats were used to examine the effectiveness of the interleukin-1 receptor antagonist against the fever induced by interleukin-1 and endotoxin. Although inactive by itself, the antagonist (three 1-micrograms bolus injections at 10-min intervals), injected into the third ventricle, attenuated the febrile response to a subsequent intracerebroventricular bolus of interleukin-1. The rise in prostaglandin E2 levels in cerebrospinal fluid, which is a characteristic feature of fever, was curtailed as well. The interleukin-1 antagonist had little or no inhibitory effect on the response to an intracerebroventricular bolus of endotoxin, even though a higher dose was employed (2-micrograms bolus injections given three times at 10-min intervals and six times at 30-min intervals, respectively, before and after endotoxin administration). At either dosage, the intracerebroventricular antagonist was completely ineffective against an intravenous bolus injection of interleukin-1 or endotoxin and both fever and prostaglandin E2 elevation developed unabated. We conclude that brain receptors mediating the pyrogenic action of centrally injected interleukin-1 are susceptible to the antagonist. The same receptors, however, are seemingly not activated by systemic pyrogens. Our findings are consistent with the concept of circulating interleukin-1 acting outside the blood-brain barrier in the normal sequence of fever.
Coceani
F
F
Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Lees
J
J
Redford
J
J
Bishai
I
I
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002415:Cats; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D007275:Injections, Intravenous; D007375:Interleukin-1; D008297:Male; D011749:Pyrogens / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins
D007375:Interleukin-1; D011749:Pyrogens; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D015232:Dinoprostone