Human interleukin-1 induces a rapid relaxation of the rabbit isolated mesenteric artery.
1. Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin-1 (IL-1) of the alpha or beta types. The effect was observed within 10 min, was optimal 32 min after the application of the cytokines and concentration-dependent (12-290 pM). 2. IL-1 alpha and IL-1 beta were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to IL-1 beta 163-171 was approximately one million fold less active than IL-1 beta. The tripeptide Lys-D-Pro-Thr, an analogue of IL-1 beta 193-195, was inactive as an antagonist of IL-1 beta on the preparation. 3. Indomethacin (2.8 microM) prevented or acutely reversed IL-1-induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10 microM) or the removal of endothelium had no effect on relaxations elicited by IL-1 beta. 4. The preparation exhibited some selectivity for IL-1 as recombinant human tumour necrosis factor-alpha (TNF-alpha), IL-2 or IL-6 failed to influence it. TNF-alpha was not synergistic with a subthreshold concentration of IL-1 beta. 5. Immunoreactive 6-keto-prostaglandin F1 alpha and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL-1 beta as compared to controls. 6. A supernatant of lipopolysaccharide-stimulated human monocytes produced a relaxation of the preparation with a profile similar to that produced with IL-1s and there was a good quantitative agreement between the extent of the relaxation and the enzyme immunoassay measurements of IL-1 alpha and IL-1 beta in the supernatant.Furthermore the relaxation of crude monocyte IL-i was prevented by preincubating with antibodies to IL-l alpha and IL-1 beta. This experiment illustrates the possible use of the preparation for bioassay of IL-1. 7. It is concluded that either form of IL-I relaxes the precontracted rabbit mesenteric artery by a prostaglandin-dependent, nitric oxide-independent mechanism. The model is also useful for distinguishing the mechanism of IL-1-induced hypotension in vivo in rabbits.
Marceau
F
F
Centre de recherche de l'Université Laval, Hôtel-Dieu de Québec, Canada.
Petitclerc
E
E
DeBlois
D
D
Pradelles
P
P
Poubelle
P E
PE
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits
D016207:Cytokines; D007375:Interleukin-1; D010446:Peptide Fragments; D011453:Prostaglandins; D010656:Phenylephrine