Volume 103, Issue 2 p. 1367-1372
Free Access

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

François Marceau

François Marceau

Centre de recherche de l'Université Laval, Hôtel-Dieu de Québec, Québec, Canada G1R 2J6

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Eric Petitclerc

Eric Petitclerc

Centre de recherche de l'Université Laval, Hôtel-Dieu de Québec, Québec, Canada G1R 2J6

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Denis DeBlois

Denis DeBlois

Centre de recherche de l'Université Laval, Hôtel-Dieu de Québec, Québec, Canada G1R 2J6

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Philippe Pradelles

Philippe Pradelles

Département de biologie, CEN-Saclay, France

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Patrice E. Poubelle

Patrice E. Poubelle

Centre de recherche Inflammation et Immunologie-Rheumatologie, Centre Hospitalier de l'Université Laval, Ste-Foy, Canada G1V 4G2

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First published: June 1991
Citations: 31

Abstract

  • 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 F 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.