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

Abstract

1 Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin-1 (IL-1) of the a or fi types. The effect was observed within 10min, was optimal 32 min after the application of the cytokines and concentration-dependent (12-290 pM).2 IL-la and IL-1i were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to [163][164][165][166][167][168][169][170][171] was approximately one million fold less active than IL-ifl. The tripeptide Lys-D-Pro-Thr, an analogue of was inactive as an antagonist of IL-1if on the preparation.3 Indomethacin (2.8pM) prevented or acutely reversed IL-1-induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10piM) or the removal of endothelium had no effect on relaxations elicited by IL-if,. 4 The preparation exhibited some selectivity for IL-1 as recombinant human tumour necrosis factor-a (TNF-a), IL-2 or IL-6 failed to influence it. TNF-a was not synergistic with a subthreshold concentration of IL-ifl. 5Immunoreactive 6-keto-prostaglandin Fl, and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL-if? 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-Is and there was a good quantitative agreement between the extent of the relaxation and the enzyme immunoassay measurements of IL-la and IL-1if in the supernatant. Furthermore the relaxation of crude monocyte IL-i was prevented by preincubating with antibodies to IL-la and IL-1if. 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.

Mode of action of thrombin in the rabbit aorta

“…The vessels were cut into rings (2-3 mm width), suspended between a metal hook and a thread loop under a basal tension of 2 g in 5 ml organ chambers containing oxygenated (95% 02:5% C02) and warmed (37"C) Krebs solution (Marceau et al, 1991). Their responses to agents were recorded isometrically as described previously (Bouthillier et al, 1987).…”

KdPT, a Tripeptide Derivative of α-Melanocyte–Stimulating Hormone, Suppresses IL-1β–Mediated Cytokine Expression and Signaling in Human Sebocytes

“…KDPT, however, does not appear to act as a simple or uniform IL-1b antagonist because the peptide did not have antipyretic activity against IL-1b in the rabbit pyrogen test (21). It was also inactive in the IL-1b-evoked relaxation of rabbit isolated mesenteric artery (23). So far, little research on KDPT has been conducted; consequently, the anti-inflammatory potential of this substance remains largely elusive.…”

Peripheral analgesic activities of peptides related to α‐melanocyte stimulating hormone and interleukin‐1β193–195

“…In contrast, the six other peptides tested had analgesic activity against PGE2 with the same order of potency as against IL-lP. The capacity of Lys-Pro-Val and Lys-D-Pro-Val but not Lys-D-Pro-Thr and D-Lys-Pro-Thr to inhibit PGE2-evoked hyperalgesia suggests that the analgesic effect of the threonine compounds might be specific to IL-ill although there is no evidence that these tripeptides compete for IL-I receptors since Lys-D-Pro-Thr was not an antagonist of IL-1p-evoked fever or stimulation of EL-4 mouse thymoma cells (Ferreira et al, 1988) or of IL-I-evoked relaxation of rabbit isolated mesenteric artery (Marceau et al, 1991).…”