Priming and induction of eosinophil trafficking in guinea‐pig cutaneous inflammation by tumour necrosis factor α

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Abstract
Tissue eosinophilia is a hallmark of allergic and parasitic diseases. Priming mechanisms may play an important role in mediating the process of eosinophil accumulation in these conditions. We have previously shown that blockade of tumour necrosis factor α (TNFα) inhibited the capacity of lipopolysaccharide to prime skin sites for chemoattractant‐induced eosinophil recruitment. The present study was carried out to investigate the capacity of TNFα to prime an inflammatory site for enhanced eosinophil accumulation. Initial experiments investigated the capacity of TNFα itself to induce eosinophil accumulation. Intradermal injection of murine TNFα (10–300 ng per site) in the guinea‐pig induced significant accumulation of 111In‐eosinophils. Kinetic studies showed the response to be delayed in onset and inhibited by cycloheximide, consistent with a dependency on protein synthesis. Trafficking of 111In‐eosinophils to sites treated for 2 h with TNFα (10–100 ng per site) was inhibited by monoclonal antibodies (mAbs) against β2 or α4 integrins. Intradermal injection of a low dose (3 ng) of TNFα (which by itself had no significant effect on eosinophil trafficking) prior to chemoattractants or antigen in sensitized skin sites, induced significant priming of eosinophil accumulation. Recruitment of both 111In‐eosinophils and endogenous eosinophils was enhanced. Trafficking to TNFα‐primed responses was dependent on protein synthesis and β2 integrins. In contrast, the α4 integrin mAb failed to inhibit the TNFα primed response. Thus, TNFα can induce and also prime eosinophil recruitment in guinea‐pig skin. Our results provide further evidence that this cytokine may be an important mediator of allergic‐ or parasite‐induced eosinophilic inflammation. British Journal of Pharmacology (1998) 125, 1228–1235; doi:10.1038/sj.bjp.0702224