REPEATED ELICITATION OF CONTACT HYPERSENSITIVITY INDUCES A SHIFT IN CUTANEOUS CYTOKINE MILIEU FROM A T-HELPER CELL-TYPE-1 TO A T-HELPER CELL-TYPE-2 PROFILE

We previously demonstrated that repeated application of 2,4,6-trinitro -1-chlorobenzene resulted in a site-restricted shift in the time cours e of Ag-specific hypersensitivity responses from a typical delayed-typ e to an early-type response, Here we demonstrated that the cutaneous m icroenvironment at the time of Ag presentation to T cells in the elici tation, but not the induction, phase of contact hypersensitivity is re sponsible for the shift, To investigate the differences in the cutaneo us cytokine milieu between the acute and chronic phases of contact hyp ersensitivity, sequential cytokine dynamics after 2,4,6-trinitro-1-chl orobenzene application were assessed in the acute vs chronic lesions, In the acute lesions, increased mRNA levels for IFN-gamma and IL-2 wer e rapidly detected at 1 h and remained elevated at 12 h, while mRNA ex pression for IL-4 and IL-10 was minimally up-regulated between similar to 12 and 24 h, In chronic lesions, high levels of constitutive expre ssion of IL-4 mRNA were observed and IL-10 mRNA was dramatically up-re gulated at 1 similar to 3 h in an Ag-specific fashion, whereas the exp ression of Th1-type cytokines was markedly reduced, Increased mRNA lev els for Th2-type cytokines in the chronic lesions was also reflected a t the protein level, These results indicate that repeated elicitation with Ag alters the balance of cytokines released locally, with a shift toward Th2-dominated responses, which would represent the natural evo lution processes directed toward reducing a more deleterious Th1 respo nse.