IL-5 production by CD4⁺ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A

Abstract

IL-5 was produced in vitro by peripheral blood mononuclear cells (PBMC) of mite-sensitive atopic patients upon challenge with specific allergen, while PBMC of healthy controls produced essentially no IL-5. Stimuli delivered by the combination of phorbol ester and Ca2+ ionophore induced marked IL-5 production by PBMC obtained from atopic and non-atopic asthmatics, suggesting that both protein kinase C and Ca2+ influx are required for IL-5 production. CD2- or CD4-bearing cell depletion almost completely removed IL-5-producing cells while CD8-bearing cell depletion rather enriched them. These findings indicate that CD4+ T cells are the principal source of IL-5 in PBMC. The capacity of PBMC of atopic asthmatics, non-atopic asthmatics and healthy controls to produce 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 IFN-gamma) were not significantly different among the three groups. Dexamethasone, FK506 and cyclosporin A suppressed IL-5 production in vitro in a dose-dependent manner. Clear dose-dependent suppression of IL-5 gene expression 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 pathogenesis of bronchial asthma and the clinical importance of its regulation.

Transcriptional Regulation of IL-5 Gene by Nontransformed Human T Cells Through the Proximal Promoter Element.

“…The intensity of IL-5 mRNAexpression correlated well with that of eosinophilic infiltration, whereas that of IL-3 and GM-CSF did not (12). Wehave reported that IL-5 production by CD4+T cells of asthmatic patients is significantly enhanced compared to that of healthy controls (13). Several experimental asthma models revealed that administration of anti-IL-5 neutralizing antibody inhibited the recruitment of eosinophils into the lung and abrogated the late phase bronchoconstriction (14)(15)(16)(17), clearly indicating the essential role of IL-5 in the late phase asthmatic response.…”

“…Con A blast lymphocytes Peripheral blood mononuclear cells (PBMC)were prepared by Ficoll-Paque density gradient centrifugation as described previously (13). Cells (2xlO6/ml) were cultured with Con A (3 (ig/ml) in RPMI 1,640 medium containing 10% fetal calf serum (FCS) for 3 days.…”

Increased vascular endothelial growth factor in acute eosinophilic pneumonia

“…The authors hypothesised that the decreases in eosinophils, IL-5 and VEGF levels were caused by the following: IL-5 synthesis by peripheral T-helper lymphocytes is inhibited by glucocorticoids, which has been demonstrated in vitro [30,31]; eosinophils release the VEGF protein product following stimulation with GM-CSF or IL-5, a process sensitive to inhibition by glucocorticoids. Glucocorticoids both suppressed the VEGF product released from eosinophils and diminished the steady-state levels of eosinophil VEGF mRNA [15].…”

Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells

“…The purpose of the present study was to determine whether or not erythromycin and its fourteen-member analogue, clarithromycin, suppress ET-1 expression and release in human airway epithelial cells, and to compare their potency with other antiasthma drugs including theophylline, β-agonist salbutamol, a glucocorticosteroid dexamethasone, and a potent macrolide immunosuppressant, FK506 [15].…”