Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-γ–inducible protein 10 expression in asthmatic airway mucosa - 18/08/11
, Jamila Chakir, PhD b
Address for reprints: Qutayba Hamid, MD, PhD, Meakins-Christie Laboratories, 3626 St Urbain, Montreal, Quebec H2X 2P2, Canada.Montreal and Ste-Foy, Quebec, Canada
Abstract |
Background |
Cytokines and chemokines have been implicated in the pathogenesis of asthma. Inhaled corticosteroids have been shown to decrease the number of eosinophils and to downregulate TH2 cytokines but to increase neutrophils. The effect of corticosteroids on chemokine expression in asthma has not yet been investigated.
Objective |
We sought to investigate the effect of a 2-week course of oral corticosteroid (methylprednisolone, 40 mg/d) on the expression of CXC chemokines (IL-8 and IFN-γ–inducible protein 10 [IP-10]) and CC chemokines (eotaxin and monocyte chemotactic proteins [MCPs] 1-4) in endoscopic biopsy specimens of 13 patients with moderate-to-severe asthma.
Methods |
CD3, major basic protein, and elastase immunoreactivities were monitored before and after treatment by using immunocytochemistry. Eotaxin, IL-8, IP-10, MCP-1, MCP-2, MCP-3, and MCP-4 mRNA expression in epithelium and submucosa were studied by using in situ hybridization.
Results |
Corticosteroids reduced the number of CD3-positive T cells and major basic protein–positive eosinophils (P < .05), whereas the number of neutrophils were increased (P < .05). Corticosteroids also reduced the number of eotaxin (P < .05), MCP-3, and MCP-4 mRNA–positive cells (P < .001) in the epithelium and subepithelium. However, corticosteroids caused a significant increase in the epithelial expression of IL-8 (P < .001), IP-10 (P < .05), and MCP-2 mRNAs (P < .01). Corticosteroids had no effects on MCP-1 mRNA expression.
Conclusion |
Our results demonstrate the dual nature of corticosteroids. Although corticosteroids can downregulate the expression of some asthma-associated chemokines, such as eotaxin, MCP-3, and MCP-4, they can also upregulate the expression of other chemokines, including IL-8, IP-10, and MCP-2. The failure of oral corticosteroids to inhibit IL-8 mRNA expression might contribute to persistent airway neutrophilia observed in patients with moderate-to-severe asthma, despite treatment with corticosteroids.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, chemokines, IL-8, eotaxin, bronchial epithelial cell, corticosteroids
Abbreviations used : GR, ICS, IP-10, MBP, MCP
Plan
Vol 115 - N° 2
P. 280-286 - février 2005 Retour au numéro
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