Effects of interleukin-1 receptor antagonist on three types of responses to interleukin-1 in rabbit isolated blood vessels

• Published in: Journal of cardiovascular pharmacology Vol. 19; no. 5; p. 821
• Main Authors: Petitclerc, E, Abel, S, deBlois, D, Poubelle, P E, Marceau, F
• Format: Journal Article
• Language: English
• Published: United States 01-05-1992
• Subjects: Animals; Blood Vessels - drug effects; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Dose-Response Relationship, Drug; Iloprost - pharmacology; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - pharmacology; Mesenteric Arteries - drug effects; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Norepinephrine - pharmacology; Phenylephrine - pharmacology; Proteins - pharmacology; Rabbits; Receptors, Immunologic - antagonists & inhibitors; Receptors, Interleukin-1; Recombinant Proteins - pharmacology; Sialoglycoproteins; Substance P - pharmacology; Vasoconstriction - drug effects; Vasodilation - drug effects
• ISSN: 0160-2446

Interleukin-1 receptor antagonist (IRA) is a secretory product of human monocytes or related cell lines that acts as a pure interleukin-1 (IL-1) antagonist in several bioassays. IRA administration was reportedly a life-saving intervention in rabbits injected with lethal doses of bacterial lipopolysaccharide (LPS). We report the inhibitory effect of IRA on three distinct types of vascular responses to IL-1 in rabbit isolated blood vessels. The rabbit isolated superior mesenteric artery, when precontracted with phenylephrine, relaxed in a sustained manner in less than 30 min following application of recombinant interleukin-1 beta (12-290 pM), and this was a prostaglandin (PG)-dependent and endothelium-independent process. IRA (human recombinant sequence; 0.9-15 nM) behaved as an antagonist of IL-1 alpha or IL-1 beta, based on the surmountability and the concentration dependence, but could only prevent the effect of IL-1, not reverse it. IRA had no direct effect on the preparation and did not influence the acute relaxing effect elicited by substance P or iloprost, a PGI2 mimetic. Exposure to IL-1 beta depressed the response to noradrenaline (NA) in several hours in rabbit aorta rings. The inhibitory effect of IL-1 beta was endothelium and prostaglandin independent, but was prevented by a treatment with NG-nitro-L-arginine (a nitric oxide synthesis inhibitor), cycloheximide, dexamethasone, or IRA. Using the residual NA-induced contraction as a quantification of the IL-1 agonist effect, IRA was a very potent antagonist of IL-1 beta but was not totally surmountable.