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

Br J Pharmacol. 1991 Jun;103(2):1367-72. doi: 10.1111/j.1476-5381.1991.tb09795.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / pharmacology
  • Electric Stimulation
  • Female
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Male
  • 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
  • Phenylephrine / pharmacology
  • Prostaglandins / metabolism
  • Rabbits

Substances

  • Cytokines
  • Interleukin-1
  • Peptide Fragments
  • Prostaglandins
  • Phenylephrine