CYCLOPHOSPHAMIDE-INDUCED BLOOD AND TISSUE EOSINOPHILIA IN CONTACT SENSITIVITY - MECHANISM OF HAPTEN-INDUCED EOSINOPHIL RECRUITMENT INTO THESKIN

The mechanism leading to selective production and accumulation of eosi nophils in certain allergic skin diseases is unknown. Cyclophosphamide treatment (150 mg/kg) of BALB/c mice 48 h before sensitization with p icryl chloride (PCl) resulted in striking blood and tissue eosinophili a, maximal at 13 days. Blood eosinophilia was not induced by the sensi tization with oxazolone and 2,4-dinitrofluorobenzene. Challenge with 1 % PCl, but not croton oil caused preferential eosinophil accumulation into the dermis, which was associated with the enhanced expression of vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells. Intra veneous administration of anti-VCAM-1 monoclonal antibody abrogated eo sinophil infiltration. In this murine model, we examined the role of s everal cytokines, including chemokines in inducing selective tissue eo sinophilia in vivo. Local administration of antibodies against interle ukin (IL)-1 beta, IL-4, tumor necrosis factor (TNF)-alpha, and RANTES, but not against IL-5 before challenge inhibited hapten-induced eosino phil recruitment. Intradermal injection of recombinant (r)IL-1 beta, r IL-4, rTNF-alpha, rRANTES, and rMIP-1 alpha induced marked eosinophil accumulation. Nonetheless, intradermal rIL-5 was not a chemoattractant for eosinophils in vivo. Our findings suggest that IL-1 beta, IL-4, T NF-alpha, and RANTES contribute to the selective accumulation of eosin ophils in contact sensitivity reaction. Although circulating IL-5 can activate eosinophils and prolong their survival, locally secreted IL-5 is not crucial for inducing eosinophil recruitment into the skin.