The effect of treatment with oral corticosteroids on asthma symptoms and airway inflammation.

Abstract

To improve understanding of the mechanisms of action of oral corticosteroids in asthma, we have conducted a double-blind, placebo-controlled study with prednisolone (20 mg for 2 wk followed by 10 mg for 4 wk) or placebo in 14 and 13 atopic corticosteroid-naive asthmatic subjects, respectively. Before and after treatment subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy. Treatment with prednisolone, but not placebo, significantly reduced asthma symptoms (from mean +/- SEM total weekly score of 34 +/- 6.2 to 15.7 +/- 3.2, p = 0.02) and albuterol usage (from mean +/- SEM number of puffs/wk of 29.7 +/- 6.2 to 18.2 +/- 3.7, p = 0.01) and significantly increased FEV1 (from 89.8 +/- 4.4% to 99.3 +/- 4.1% of predicted, p = 0.03). There were no significant changes in inflammatory or epithelial cell counts, levels of T-cell activation or albumin concentration in BAL. However, immunohistochemistry of bronchial biopsies showed that in the submucosa prednisolone significantly decreased numbers of mast cells by 62% (from median 45 to 17/mm2, p = 0.01), eosinophils by 81% (from median 30.1 to 5.7/mm2, p = 0.004), and CD4+ T-cells by 68% (from median 64.6 to 18.5/mm2, p = 0.02). In the epithelium only the reduction in the numbers of eosinophils was significant (from median 1.1 to 0/mm of epithelium, p = 0.02). There were no significant changes in any cell counts in the subjects receiving placebo, and comparison of the changes between the treatment groups identified a significant prednisolone-related reduction in submucosal eosinophil and mast cell counts (p = 0.003 and 0.03, respectively). The temporal association between the clinical and physiologic improvement, and the correlation between the magnitude of change in CD4+ T-cell counts in the submucosa and increase in PC20 methacholine (rs = 0.60, p = 0.049) suggests that the reduction in airways inflammatory cell numbers underlies the clinical efficacy of oral corticosteroids.

Effect of Dexamethasone on Lymphocyte Subpopulations in Premature Infants with Bronchopulmonary Dysplasia

“…Recently, it was reported that CD4 cell numbers were decreased in bronchial biopsies from asthmatics treated with oral prednisolone. 27 The authors speculated that CD4 cells may play an important part in asthmatic inflammation, and we believe our data suggest an analogous role for CD4 cells in BPD.…”

Role of B7-CD28/CTLA-4 Costimulation and NF-κB in Allergen-Induced T Cell Chemotaxis by IL-16 and RANTES

“…Both cytokines are partly dependent on cell-cell interaction involving the costimulatory molecule CD28 and its ligand B7. The observed inhibitory effect of dexamethasone on the production of IL-16 and RANTES and on the chemotactic activity is in keeping with the ability of corticosteroids to reduce the numbers of CD4 ϩ T cells in the airways mucosa (25). Finally, in showing a significant inhibitory effect of the proteasome inhibitor PSI on IL-16 generation and T cell chemotactic activity, we have shown a role for NF-B in partially regulating these components of the inflammatory response in asthma.…”

AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity

“…Throughout the past several years the compliant use of inhaled steroids has proven to be important in the control of atopic asthma. [7][8][9][10][11] However, because of continued development of steroid resistance and side effects that have been attributed to long-term steroid use, other alternatives have been explored. In particular, an attractive set of targets is the chemokine family members and their receptors that are responsible for the recruitment of particular subsets of leukocytes to the inflamed lung.…”