Background: Interleukin-5 (IL-5) is known to play a major role in regulating eosinophil function in atopic diseases, including bronchial asthma. Glucocorticoids are most effective agents for treating these diseases. However, their mechanism remains unclear. We examined the effects of glucocorticoids on the production and gene expression of IL-5 in atopic patients and normal subjects.
Methods: Human peripheral blood mononuclear cells (PBMCs) in five atopic and four normal subjects were cultured with phytohemagglutinin and phorbol 12-myristate 13-acetate (PMA) in the presence of dexamethasone. IL-5 secreted by PBMCs was assayed by ELISA. Gene expression of IL-5 by PBMCs was assessed semiquantitatively by sequential reverse transcription-polymerase chain reaction, and Southern blot analysis.
Results: Phytohemagglutinin/PMA-stimulated PBMCs from all atopic patients and three normal subjects secreted detectable amounts of IL-5, which were suppressed by dexamethasone in a dose-dependent manner, with 85.8% suppression at 10(-6) mol/L. Gene expression of IL-5 was detected by reverse-transcription polymerase chain reaction in PBMCs from all subjects, even when not stimulated; was increased by stimulation; and was suppressed by dexamethasone. The concentration of dexamethasone resulting in 50% inhibition in IL-5 gene expression did not differ between atopic patients and normal subjects.
Conclusion: These findings indicate that dexamethasone suppressed IL-5 production in atopic human PBMCs through an inhibitory action on the gene expression. These results suggest that the suppression of IL-5 production through the suppression of IL-5 gene expression is one of the most important mechanisms by which glucocorticoids inhibit eosinophil functions in the treatment of atopic diseases, including bronchial asthma.