UP-REGULATION OF FORMYL-PEPTIDE AND INTERLEUKIN-8-INDUCED EOSINOPHIL CHEMOTAXIS IN PATIENTS WITH ALLERGIC-ASTHMA

Background: The cytokine granulocyte-macrophage colony-stimulating fac tors, interleukin-3 and interleukin-5, are important modulators of eos inophilia and eosinophil function. In particular, eosinophil chemotaxi s is very sensitive to cytokine priming. Methods: We evaluated chemota ctic responses of eosinophils from Patients with allergic asthma. Thes e cells exhibited a primed phenotype as deduced from enhanced response s toward formyl-methionyl-leucyl-phenylalanine and platelet-activating factor and a decreased responsiveness toward granulocyte-macrophage c olony-stimulating factor. Bronchoprovocation of patients with allergic asthma with allergen was performed as a possible means to enhance in vivo priming. Results: Indeed, eosinophils isolated 3 hours after alle rgen challenge exhibited a more pronounced primed phenotype, which was reflected by an induction of responsiveness towards interleukin-& Eos inophil responses induced by platelet-activating factor, formyl-methio nyl-leucyl-phenylalanine, complement fragment C5a, interleukin-3, inte rleukin-5, and granulocyte-macrophage colony-stimulating factor were n ot significantly altered after allergen challenge. Conclusion: These d ata provide further evidence that eosinophils are already primed in th e peripheral blood of individuals with allergic asthma. This is most l ikely due to the presence of circulating cytokines in the peripheral b lood of those individuals. This in vivo priming results in selective u pregulation and downregulation of responses toward various chemotaxins , which may be released in the lungs during allergic inflammation.