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IL-4 has been implicated in the pathogenesis of a number of allergic inflammatory disease states where the accumulation of eosinophils is a prominent feature. The aim of the present study was to use an isotopic in vivo model to investigate the ability of recombinant rat IL-4 in inducing eosinophil accumulation in rat skin. 111In-eosinophil accumulation in response to intradermally injected IL-4 was measured during 0 to 4 h, 24 to 28 h, and 48 to 52 h. Accumulation was detected during the first two periods, but not at the later time point. The accumulation during 24 to 28 h, which was dose dependent, was investigated in detail. Administration i.v. of an anti-rat VCAM-1 mAb, but not an anti-rat ICAM-1 mAb, inhibited the accumulation of 111In-eosinophils induced by IL-4 (maximum inhibition, 80%). Further, when the 111In-eosinophils were pretreated in vitro with an anti-beta 2 integrin mAb, an anti-alpha 4 integrin mAb, or a combination of both mAbs, before their injection into recipient rats, the IL-4-induced cell accumulation was inhibited by 63, 60, and 74%, respectively. Finally, coadministration of IL-4 with the soluble TNF receptor (p55)-IgG fusion protein significantly reduced the 111In-eosinophil accumulation induced by the cytokine, and TNF-alpha was detected in IL-4-injected skin sites by both immunostaining and bioassay. Our results demonstrate that IL-4 is a potent inducer of eosinophil accumulation in vivo, the response being dependent on the endogenous generation of TNF-alpha, beta 2 integrins, and alpha 4 integrin/VCAM-1 interactions.

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

06/1998

Volume

160

Pages

5637 - 5645

Addresses

Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.

Keywords

Eosinophils, Skin, Animals, Rats, Rats, Sprague-Dawley, Indium Radioisotopes, Tumor Necrosis Factor-alpha, Immunoglobulin G, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Integrin alpha4, Antigens, CD18, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Fusion Proteins, Antigens, CD, Interleukin-4, Antibodies, Monoclonal, Injections, Intradermal, Cell Adhesion, Cell Movement, Dose-Response Relationship, Immunologic, Solubility, Time Factors, Male