title: Corticosteroid resistance in mild asthma: markers of persistent inflammation.
abstract: BACKGROUND
  Bronchial hyperresponsiveness (BHR) is an important feature of asthma. Glucocorticosteroids (GCS) reduce BHR, probably by suppressing allergic inflammation. There are, however, two groups of asthmatics with either GCS-responsive or non-responsive BHR to methacholine. We investigated the mechanism of non-GCS-responsive BHR in mild asthma.
  
  
  METHODS
  Non-GCS-responsive BHR asthma was defined as failure of reduction of BHR to methacholine after a 2-week course of oral prednisolone (30 mg/day). The expression of interleukin (IL)-4, IL-5, IFN-gamma mRNA in peripheral blood mononuclear cells, eosinophil count, serum cortisol, eosinophilic cationic protein (ECP), and spirometry were measured in five non-GCS-responsive BHR asthmatics and six patients with GCS-responsive BHR asthma before and after prednisolone therapy.
  
  
  RESULTS
  With the exception of serum ECP and expression of IL-5 mRNA, no significant differences were observed between GCS-responsive BHR and non-GCS-responsive BHR asthma. The mean ECP level was significantly higher in non-GCS-responsive BHR than in GCS-responsive BHR asthma before and after prednisolone therapy. Interleukin-5 mRNA was detected in all asthmatics before prednisolone therapy; however, after prednisolone therapy, IL-5 mRNA was only detected in non-GCS-responsive BHR asthmatics.
  
  
  CONCLUSIONS
  Our findings suggest that activation of eosinophils appears to persist in some asthmatics with non-GCS-responsive BHR due to continuous IL-5 production by lymphocytes.
authors.affiliation: The Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsuse
authors.forename: T
authors.initials: T
authors.lastname: Shimoda
authors.forename: N
authors.initials: N
authors.lastname: Matsuo
authors.forename: Y
authors.initials: Y
authors.lastname: Obase
authors.forename: S
authors.initials: S
authors.lastname: Asai
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001250:Asthma, Exercise-Induced / Q000188:drug therapy / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D004351:Drug Resistance; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D005938:Glucocorticoids; D015848:Interleukin-5; D007371:Interferon-gamma; D011239:Prednisolone