Interleukin-10–Secreting “Regulatory” T Cells Induced by Glucocorticoids and β₂-Agonists

Abstract

Greater clinical benefit in controlling the symptoms of asthma is frequently observed through combining moderate doses of inhaled glucocorticoids together with long-acting beta(2)-agonists, as compared with increasing glucocorticoid dosage alone. To address in vitro whether glucocorticoids plus beta(2)-agonists, compared with glucocorticoids alone, have greater inhibitory activity on CD4+ T cell responses to allergen, peripheral blood CD4+ T cell responses to allergen were compared in the presence or absence of the glucocorticoid fluticasone proprionate and the short- and long-acting beta(2)-agonists salbutamol and salmeterol, respectively. Fluticasone proprionate inhibited interleukin (IL)-5 and IL-13 and enhanced IL-10 synthesis in allergen-stimulated cultures in a concentration-dependent manner. Salmeterol, but not salbutamol, inhibited IL-5 and IL-13 and enhanced IL-10 synthesis in these cultures. When used in combination the two drugs demonstrated an additive effect on this pattern of cytokine production. Allergen-specific T cell lines induced in the presence of salmeterol and fluticasone proprionate inhibited IL-5 and IL-13 production by allergen-specific Th2 cell lines in an IL-10-dependent manner. Thus fluticasone proprionate and salmeterol increased IL-10 and reduced Th2 cytokine synthesis additively in allergen stimulated human CD4+ T cells.

Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients

“…However, it may also be possible to achieve similar cooperative effects between glucocorticoids and other drugs for induction of IL-10-secreting Tregs. Indeed, our recent studies demonstrate a similar capacity upon combining glucocorticoids with long-acting β 2 -agonists to induce an IL-10-secreting Treg profile (37).…”

Regulatory T cells in bronchial asthma

“…Other drug combinations also clearly promote IL-10 secreting Treg populations. For example, glucocorticoids in combination with long-acting b2 agonists can also induce allergen-specific regulatory T cells when used in culture of naı¨ve T cells from the peripheral blood of asthmatics (121), although this drug combination was not as effective as the original dexamethasone plus calcitriol combination. These data further suggest that vitamin D may be important in immune homeostasis in the lung.…”

Enhanced Frequency of CD18- and CD49b-Expressing T Cells in Peripheral Blood of Asthmatic Patients Correlates with Disease Severity

“…It could be hypothesized that steroid treatment of these patients might contribute to the loss of the regulatory function of these cells. However, it has been reported that dexamethasone induces, rather than decreases, the production of IL-10 by human CD4+T cells in vitro [26,27,28]. Moreover, Matsumoto et al [29] have shown that production levels of IL-10 by circulating CD4+ CD45RO+ T cells in response to stimulation with dexamethasone did not differ between mild and severe asthmatic patients and that, although a significantly lower frequency of IL-10-producing T cells was observed in uncontrolled as compared with controlled severe asthmatics, this decrease could not be explained by the effect of high-dose inhaled corticosteroid medication.…”