Human interleukin‐1 induces a rapid relaxation of the rabbit isolated mesenteric artery

• Published in: British journal of pharmacology Vol. 103; no. 2; pp. 1367 - 1372
• Main Authors: Marceau, François, Petitclerc, Eric, DeBlois, Denis, Pradelles, Philippe, Poubelle, Patrice E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-1991; Nature Publishing
• Subjects: Animals; Biological and medical sciences; Cardiovascular system; Cytokines - pharmacology; effect of interleukin‐1; Electric Stimulation; Female; Humans; In Vitro Techniques; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - pharmacology; Interleukin‐1‐induced vascular relaxation; Male; Medical sciences; Mesenteric Arteries - drug effects; Monocytes - drug effects; Monocytes - physiology; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Phenylephrine - pharmacology; Prostaglandins - metabolism; prostaglandin‐induced vascular relaxation; rabbit mesenteric artery; Rabbits; Vasodilator agents. Cerebral vasodilators; Human; Prostaglandin; Arachidonic acid derivatives; Cytokine; Rabbit; Smooth muscle; Lagomorpha; Muscle contraction; In vitro; Vertebrata; Mesenteric artery; Mammalia; Peptide fragment; Analog; Animal; Interleukin 1; Circulatory system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1991.tb09795.x

1
Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin‐1 (IL‐1) of the α or β 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‐1α and IL‐1β were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to IL‐1β 163–171 was approximately one million fold less active than IL‐1β. The tripeptide Lys‐d‐Pro‐Thr, an analogue of IL‐1β 193–195, was inactive as an antagonist of IL‐1β on the preparation.
3
Indomethacin (2.8 μm) prevented or acutely reversed IL‐1‐induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10 μm) or the removal of endothelium had no effect on relaxations elicited by IL‐1β.
4
The preparation exhibited some selectivity for IL‐1 as recombinant human tumour necrosis factor‐α (TNF‐α), IL‐2 or IL‐6 failed to influence it. TNF‐α was not synergistic with a subthreshold concentration of IL‐1β.
5
Immunoreactive 6‐keto‐prostaglandin F1α and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL‐1β 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‐1α and IL‐1β in the supernatant. Furthermore the relaxation of crude monocyte IL‐1 was prevented by preincubating with antibodies to IL‐1α and IL‐1β. This experiment illustrates the possible use of the preparation for bioassay of IL‐1.
7
It is concluded that either form of IL‐1 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.