EVIDENCE THAT CYCLOSPORINE-A AND DEXAMETHASONE INHIBIT ALLERGIC AIRWAY EOSINOPHILIC INFLAMMATION VIA SUPPRESSION OF INTERLEUKIN-5 SYNTHESISBY T-CELLS

1 We have recently demonstrated that airway eosinophilic inflammation can be transferred to unprimed mice by infusing interleukin (IL)-5-pro ducing T cell clones. Using that murine model, we performed this study to delineate the mechanism of cyclosporin A and dexamethasone to inhi bit allergic airway eosinophilic inflammation. 2 The ovalbumin-reactiv e murine T cell clones, FJ17, produced IL-2, IL-4 and IL-5 upon stimul ation with relevant antigen. In FJ17-transferred mice, messenger RNA ( mRNA) of IL-2 and IL-5 expressed in the lungs, the number of eosinophi ls in bronchoalveolar lavage fluid (BALF) was increased and the bronch ial responsiveness to acetylcholine was enhanced after antigen provoca tion. 3 Cyclosporin A (10, 100 ng ml(-1)) and dexamethasone (10, 100 n g ml-L suppressed the production of IL-5 as well as IL-2 and IL-4 by F J17 in vitro. 4 Subcutaneously administered cyclosporin A (30 mg kg(-1 )) and dexamethasone (10 mg kg-l) inhibited antigen-induced mRNA expre ssion of IL-2 and IL-5, increase of BALF eosinophils and bronchial hyp erresponsiveness of FJ17-transferred mice in vivo. The number of BALF eosinophils was correlated with the bronchial responsiveness to acetyl choline (r = 0.672). 5 The results clearly indicated that the suppress ion of IL-5 synthesis by T cells is involved in the effects of cyclosp orin A and dexamethasone to inhibit allergic airway eosinophilic infla mmation.