title: Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa.
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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Motonori
authors.initials: M
authors.lastname: Fukakusa
authors.forename: Celine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Meri K
authors.initials: MK
authors.lastname: Tulic
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fiset
authors.forename: Oday
authors.initials: O
authors.lastname: Al Dewachi
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D004804:Eosinophils / Q000473:pathology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000627:therapeutic use; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D005938:Glucocorticoids; D016209:Interleukin-8; D012333:RNA, Messenger; D008775:Methylprednisolone