Dexamethasone and cyclosporin 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 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.
Wang
J M
JM
Unité de Recherche, Hôpital Laval, Ste-Foy, Québec, Canada.
Chu
H W
HW
Bossé
M
M
St-Pierre
J
J
Boutet
M
M
Laviolette
M
M
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D000954:Antigens, Surface / Q000187:drug effects; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology*; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL
D000908:Antibodies, Fungal; D000954:Antigens, Surface; D016207:Cytokines; D003907:Dexamethasone