title: IL-1 is a potent inducer of eosinophil accumulation in rat skin. Inhibition of response by a platelet-activating factor antagonist and an anti-human IL-8 antibody.
abstract: The aim of the present study was to investigate directly and characterize the ability of IL-1 beta in inducing eosinophil accumulation in vivo. For this purpose, we studied the recruitment of 111In-labeled eosinophils in rat skin in response to intradermally injected rat rIL-1 beta. Rat rIL-1 induced a dose-dependent accumulation of 111In-labeled eosinophils, with the maximal response being detected at 5 x 10(-13) mol/site. This response was slow in onset, progressively increasing over the 4-h period investigated. Rat rIL-1 also induced a small level of edema, as measured by the local accumulation of i.v. 125I-labeled albumin, which developed with a time course similar to that of 111In-labeled eosinophil accumulation. Co-administration of the cytokine with the IL-1R antagonist, IL-1ra, or actinomycin D, significantly inhibited the 111In-labeled eosinophil accumulation, and reduced the edema formation, induced by rat rIL-1. In addition, the 111In-labeled eosinophil accumulation was significantly suppressed in animals treated with the PAF antagonist UK-74,505 or an anti-human IL-8 mAb DM/C7. These observations demonstrate for the first time that IL-1 beta is a potent inducer of eosinophil accumulation in vivo. Moreover, the results reveal that this activity of IL-1 beta is receptor mediated and dependent on the induction of proteins that may be involved in the local generation of secondary inflammatory mediators including PAF and an IL-8-like molecule. These findings are consistent with the view that endogenously generated IL-1 may play an important role in the recruitment of eosinophils at sites of allergic inflammation.
authors: Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
authors: M J
authors: MJ
authors: Sanz
authors: V B
authors: VB
authors: Weg
authors: M A
authors: MA
authors: Bolanowski
authors: S
authors: S
authors: Nourshargh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003609:Dactinomycin / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004487:Edema / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D007093:Imidazoles / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D016209:Interleukin-8 / Q000276:immunology; D007975:Leukotriene B4 / Q000502:physiology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000502:physiology; D012867:Skin / Q000166:cytology* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004095:Dihydropyridines; C507763:IL1RN protein, human; D007093:Imidazoles; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D010972:Platelet Activating Factor; D012795:Sialoglycoproteins; D003609:Dactinomycin; C073027:modipafant; D007975:Leukotriene B4; D002118:Calcium