Attenuation of the Allergen-induced Late Asthmatic Reaction by Cyclosporin A Is Associated with Inhibition of Bronchial Eosinophils, Interleukin-5, Granulocyte Macrophage Colony-Stimulating Factor, and Eotaxin

Abstract

The allergen-induced late asthmatic reaction (LAR) is associated with increases in bronchial eosinophils and basophils as well as upregulation of several eosinophil active cytokines and C-C chemokines. Cyclosporin A (CsA) was previously shown to inhibit the LAR, but not the early asthmatic reaction (EAR), and this was associated with a decrease in blood eosinophils. For these reasons, we determined whether CsA inhibited the allergen-induced increases in bronchial eosinophils, basophils, eotaxin, interleukin-5 (IL-5), and granulocyte macrophage colony-stimulating factor (GM-CSF). Subjects with a demonstrable LAR underwent bronchoscopy with biopsy and bronchoalveolar lavage (BAL) at baseline and then were randomly allocated to receive either CsA (n = 13) or placebo (n = 11) before challenge. A second bronchoscopy was performed 24 h later. The LAR, but not the EAR, was significantly attenuated in the CsA group compared with placebo (p < 0.05). CsA significantly inhibited the allergen-induced increases in IL-5 (p = 0.02) and GM-CSF (p = 0. 0028) in mRNA+ cells in BAL, and in a mAB against human activated eosinophils (EG2+) (p = 0.0227). We conclude that inhibition of the LAR by CsA may be related to its inhibitory effects on eosinophil-associated cytokines and chemokines. The beneficial effect of CsA in asthma may also be the result of inhibition of eosinophil accumulation.

Regulation of IL‐13 synthesis in human lymphocytes: implications for asthma therapy

“…*P50.05 (versus OVA challenged vehicle control). treatment, they cannot ®nd a broad practice due to their unacceptable side eects (Corrigan et al, 1996;Khan et al, 2000;Lock et al, 1996;Mori et al, 2000;Sperr et al, 1997). These agents interfere with multiple T cell functions, thereby causing generalized immunosuppression.…”

Cyclosporin A, apoptosis of BAL T-cells and expression of Bcl-2 inasthmatics

“…The study was conducted over 4 weeks, as previously described [11]. Briefly, a full clinical history was taken and examination performed at an initial assessment.…”

“…In the present study, clinical samples were used from the same patients as described in a previously published report [11]. Thus the subjects had mild atopic asthma (n=24), were sensitive to either grass pollen, house dust mite or cat dander, and were recruited from the London Chest Hospital or the Royal Brompton Hospital, London, UK.…”

“…Although NIZANKOWSKA et al [7] showed that there were no significant changes in lung function or the steroid-sparing effect in CsA-treated asthmatics, placebo-controlled studies in steroid-dependent asthma demonstrated improvement in lung function [8] and decreases in oral corticosteroid requirement [9]. Attenuation of the allergen-induced late asthmatic reaction (LAR) has also been described [10] and shown to be associated with reduced expression of eosinophil growth and chemotactic factor concentrations in BALF [11]. In the present study, the hypothesis that CsA inhibits the LAR by accelerating the apoptosis of CD3-positive cells and that this is associated with decreases in the expression of the antiapoptotic protein B-cell leukaemia/lymphoma 2 gene product (Bcl-2) was tested.…”

Exploring New Frontiers in Asthma Management for Optimal and Economic Outcomes

“…Cyclosporine, a potent immunosuppressant that inhibits the activation of T cells and other inflammatory cells, attenuates the allergen-induced late asthmatic reaction, possibly by inhibiting eosinophils and IL-5 accumulation. 33 Reductions in corticosteroid dosage requirements have been associated with oral cyclosporine use in patients with corticosteroiddependent asthma. 34 Administering cyclosporine by inhalation instead of the oral route to minimize systemic adverse effects (e.g., nephrotoxicity, immunosuppression) is a promising avenue for research.…”