The Journal of Immunology, Vol 154, Issue 3 1364-1373, Copyright © 1995 by American Association of Immunologists

ARTICLES

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

MJ Sanz, VB Weg, MA Bolanowski and S Nourshargh
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.

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.

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