IL-4 INDUCES EOTAXIN - A POSSIBLE MECHANISM OF SELECTIVE EOSINOPHIL RECRUITMENT IN HELMINTH INFECTION AND ATOPY

A common feature of some parasitic infections and allergic and atopic skin diseases is the involvement of Th2 lymphocytes and the dermal app earance of eosinophils (Eos), Because Th2 lymphocytes apparently do no t release Eo attractants, we addressed the question of whether the Th2 cytokine IL-4 induces its production in dermal fibroblasts. We theref ore stimulated fibroblasts with IL-4, HPLC investigation of supernatan ts revealed a single 80 chemotactic protein, which was purified to hom ogeneity giving a single 13-kDa band upon SDS-PAGE analyses, Peptide m apping with subsequent amino acid sequencing revealed an Eo-selective chemotaxin, which consists of a mixture of N-terminally truncated and O-glycosylated forms of the chemokine eotaxin. Other chemokines such a s RANTES, MCP-3, MCP-4, or MIP-1 alpha were not detected as Eo chemota xins under these conditions, Using reverse transcriptase-PCR technique s, we found that IL-4 dose and time dependently induces eotaxin mRNA i n dermal fibroblasts. Stimulation with IL-4 and TNF-alpha caused a 10- to 20-fold increase of the release of three biochemically different e otaxin forms, each consisting of a mixture of N-terminally truncated a nd O-glycosylated variants having the same backbone amino acid sequenc e but different specific activities, Our findings support the hypothes is that eosinophil recruitment seen in IL-4-mediated skin reactions, a t least in part, may be due to Th2 cytokine-mediated induction of eota xin in dermal fibroblasts.