Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa

J Allergy Clin Immunol. 2005 Feb;115(2):280-6. doi: 10.1016/j.jaci.2004.10.036.


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 T H 2 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-gamma-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.

MeSH terms

  • Administration, Oral
  • Adult
  • Asthma / drug therapy
  • Asthma / metabolism*
  • Asthma / pathology*
  • Chemokine CXCL10
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism
  • Drug Administration Schedule
  • Eosinophils / pathology*
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / therapeutic use
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Leukocyte Count
  • Male
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / therapeutic use
  • Neutrophils / pathology
  • RNA, Messenger / metabolism
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology


  • CXCL10 protein, human
  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CC
  • Chemokines, CXC
  • Glucocorticoids
  • Interleukin-8
  • RNA, Messenger
  • Methylprednisolone