IL-5 PRODUCTION BY CD4(-CELLS OF ASTHMATIC-PATIENTS IS SUPPRESSED BY GLUCOCORTICOIDS AND THE IMMUNOSUPPRESSANTS FK506 AND CYCLOSPORINE-A() T)

IL-5 was produced in vitro by peripheral blood mononuclear cells (PBMC ) of mite-sensitive atopic patients upon challenge with specific aller gen, while PBMC of healthy controls produced essentially no IL-5. Stim uli delivered by the combination of phorbol ester and Ca2+ ionophore i nduced marked IL-5 production by PBMC obtained from atopic and non-ato pic asthmatics, suggesting that both protein kinase C and Ca2+ influx are required for IL-5 production, CD2- or CD4-bearing cell depletion a lmost completely removed IL-5-producing cells while CD8-bearing cell d epletion rather enriched them, These findings indicate that CD4(+) T c ells are the principal source of IL-5 in PBMC, The capacity of PBMC of atopic asthmatics, non-atopic asthmatics and healthy controls to prod uce IL-2, IL-4, IL-5 and IFN-gamma was compared, to find that cytokine -producing capacities other than that of IL-5 (IL-2, IL-4 and lFN-gamm a) were not significantly different among the three groups, Dexamethas one, FK506 and cyclosporin A suppressed IL-5 production in vitro in a dose-dependent manner, Clear dose-dependent suppression of IL-5 gene e xpression by FK506 was also observed, Treatment of asthmatic patients with inhaled glucocorticoid (beclomethasone dipropionate) ameliorated clinical symptoms, improved lung function and markedly suppressed IL,- 5 production by PBMC, suggesting the essential role of IL-5 in the pat hogenesis of bronchial asthma and the clinical importance of its regul ation.