IL-4-induced eosinophil accumulation in rat skin is dependent on endogenous TNF-alpha and alpha 4 integrin/VCAM-1 adhesion pathways.

Journal article

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.

Authors: Sanz, M; Marinova-Mutafchieva, L; Green, P; Lobb, R; Feldmann, M

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 160
• Issue: 11
• Pages: 5637-5645
• Publication date: 1998-06-01
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Receptors, Tumor Necrosis Factor; Antigens, CD18; Interleukin-4; Time Factors; Cell Movement; Eosinophils; Solubility; Antibodies, Monoclonal; Receptors, Tumor Necrosis Factor, Type I; Rats, Sprague-Dawley; Vascular Cell Adhesion Molecule-1; Recombinant Fusion Proteins; Immunoglobulin G; Intercellular Adhesion Molecule-1; Male; Cell Adhesion; Injections, Intradermal; Indium Radioisotopes; Integrin alpha4; Rats; Skin; Tumor Necrosis Factor-alpha; Animals; Antigens, CD; Dose-Response Relationship, Immunologic