IL-5-Producing T Cells that Induce Airway Eosinophilia and Hyperresponsiveness Are Suppressed by Dexamethasone and Cyclosporin A in Mice

Abstract

We have recently demonstrated that airway eosinophilic inflammation can be transferred to unprimed mice by infusion of IL-5-producing T cell clones. In this study, we investigated the effects of dexamethasone and cyclosporin A on the airway eosinophilic inflammation in mice transferred with T cell clones. An ovalbumin-reactive T cell clone, KW29, produced IL-5 as well as IL-2 and IL-4 upon stimulation with relevant antigen. Dexamethasone and cyclosporin A dose-dependently suppressed the production of these cytokines in vitro. The number of eosinophils recovered in the bronchoalveolar lavage fluid and the airway responsiveness to acetylcholine were increased in KW29-transferred mice after antigen provocation. Both responses were dose-dependently suppressed by the administration of dexamethasone or cyclosporin A in vivo. We concluded that airway eosinophilic inflammation can be controlled by agents capable of downregulating IL-5 production in T cells.

TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation

“…21,22 In our T H 1 model treatment with dexamethasone (4 mg/kg) did not significantly reduce the total numbers of BALF cells in comparison with the numbers observed in the vehicle-treated group. However, the analysis of the inflammatory cells in these mice revealed that the treatment dramatically reduced the numbers of lymphocytes and macrophages while not affecting the numbers of neutrophils in BALF (Fig 4, A).…”

Serum interleukin-5 levels are elevated in mild and moderate persistent asthma irrespective of regular inhaled glucocorticoid therapy

“…Although activated CD3+ T cells are the primary source of IL-5 in atopic asthma, CD8 cells are thought to be the main source in non-atopic asthma [6]. A reduction in IL-5 induced eosinophilia upon subcutaneous administration of glucocorticoids in an animal model of asthma, has been documented by Wada and associates [7]. Furthermore, oral glucocorticoids have been shown to reduce elevated serum IL-5 levels in patients with acute asthma [8].…”

Interleukin-5: a novel target for asthma therapy

“…Successful treatment of asthmatic patients with glucocorticoids or cyclosporin A is associated with significantly less mRNA production for IL-3, IL-5 and GM-CSF by CD4 + T-cells compared to non-treated controls [148,149]. These results were confirmed by reduction of pulmonary eosinophilia by treatment with dexamethasone, cyclosporin A, FK-506, nonactin and mizoribine in an asthma mouse model [150][151][152].…”