Dexamethasone and cyclosporin A modulation of cytokine expression and specific antibody synthesis in an allergic bronchopulmonary aspergillosis murine model.

Abstract

We previously demonstrated that, in C57B1/6 mice, cyclosporin A enhanced and dexamethasone inhibited the Aspergillus fumigatus-induced pulmonary eosinophilia and total IgE levels. To evaluate whether these effects were related to the modulation of T-lymphocyte recruitment and activation and cytokine expression, we performed immunohistochemical staining for T-cell surface marker CD3 and CD4, cell activation marker CD25, and cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and interleukin-5 (IL-5) on lung tissue sections from mice exposed to Aspergillus fumigatus and treated or not with dexamethasone or cyclosporin A. Dexamethasone significantly inhibited Aspergillus fumigatus-induced increased number of activated T cells and cytokine-expressing cells in parallel with a decrease in pulmonary eosinophils. In contrast, cyclosporin A did not decrease these immunological events but enhanced the lung eosinophil recruitment. Moreover, dexamethasone prevented the production of immunoglobulins against 76 and 36 kD antigen proteins and cyclosporin A against 76 and 18 kD antigen proteins. These results indicate that dexamethasone down-regulates and cyclosporin A up-regulates lung eosinophil recruitment and total IgE production, probably via the modulation of T-lymphocyte activation and GM-CSF, IL-4 and IL-5 expression. Both drugs inhibit Aspergillus fumigatus-specific antibody synthesis, but their suppressive actions are selective to different antigenic components.