DEXAMETHASONE AND CYCLOSPORINE-A MODULATION OF CYTOKINE EXPRESSION AND SPECIFIC ANTIBODY-SYNTHESIS IN AN ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS MURINE MODEL

We previously demonstrated that, in C57B1/6 mice, cyclosporin A enhanc ed and dexamethasone inhibited the Aspergillus fumigatus-induced pulmo nary eosinophilia and total IgE levels. To evaluate whether these effe cts were related to the modulation of T-Iymphocyte recruitment and act ivation and cytokine expression, we performed immunohistochemical stai ning for T-cell surface marker CD3 and CD4, cell activation marker CD2 5, and cytokines granulocyte-macrophage colony-stimulating factor (GM- CSF), interleukin-4 (IL-4) and interleukin-5 (IL-5) on lung tissue sec tions from mice exposed to Aspergillus fumigatus and treated or not wi th dexamethasone or cyclosporin A. Dexamethasone significantly inhibit ed Aspergillus fumigatus-induced increased number of activated T cells and cytokine-expressing cells in parallel with a decrease in pulmonar y eosinophils. In contrast, cyclosporin A did not decrease these immun ological 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 ant igen proteins. These results indicate that dexamethasone down-regulate s and cyclosporin A up-regulates lung eosinophil recruitment and total IgE production, probably via the modulation of T-lymphocyte activatio n 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.