Differential regulation of cytokine expression after allergen exposure of sensitized rats by cyclosporin A and corticosteroids: relationship to bronchial hyperresponsiveness.

BACKGROUND

Cyclosporin A and dexamethasone exhibit different effects on allergic airway eosinophilia and bronchial hyperresponsiveness (BHR).

OBJECTIVE

We determined whether these were related to alteration of cytokine expression, particularly with regard to the profile of Th1- versus Th2-derived cytokines.

METHODS

Brown-Norway rats sensitized with ovalbumin were administered cyclosporine or dexamethasone before ovalbumin aerosol challenge. Bronchial responsiveness was measured 18 to 24 hours after aerosol exposure. Airway cellular influx was determined by bronchoalveolar lavage and tissue immunohistochemistry. The expression of Th1 and Th2 cytokine messenger RNA (mRNA) was analyzed by reverse transcriptase-PCR.

RESULTS

Ovalbumin exposure induced significant BHR, with increases in eosinophils, lymphocytes, and neutrophils in bronchoalveolar lavage fluid and an increase in eosinophils, CD2(+) and CD8(+), but not CD4(+) T cells, in the airway submucosa. IL-2, IFN-gamma, IL-4, and IL-5 mRNA expression in the lungs of sensitized ovalbumin-exposed rats was increased (P <.05) compared with controls. Cyclosporin A had no significant effect on BHR and neutrophil accumulation but reduced the number of bronchoalveolar lavage eosinophils (P <.002), airway submucosal eosinophils, and CD4(+) and CD8(+) T cells (P <.02). It also suppressed the induced mRNA expression of IL-2, IL-4, IL-5, and IFN-gamma. By contrast, the inflammatory cell influx and mRNA expression for IL-2, IL-4, and IL-5, as well as BHR, were suppressed by dexamethasone. However, an increase in IL-10 and IFN-gamma mRNA expression was found.

CONCLUSION

The differential activities of cyclosporin A and dexamethasone on inflammatory cell influx, particularly neutrophils, or cytokine expression such as IL-10 and IFN-gamma may underlie their contrasting effects on BHR.