Corticosteroid resistance in mild asthma: markers of persistent inflammation.
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.
Matsuse
H
H
The Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Shimoda
T
T
Matsuo
N
N
Obase
Y
Y
Asai
S
S
Kohno
S
S
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
D005938:Glucocorticoids; D015848:Interleukin-5; D007371:Interferon-gamma; D011239:Prednisolone