The effects of inhaled and oral corticosteroids on serum inflammatory biomarkers in COPD: an exploratory study.
BACKGROUND
Several studies suggest that inhaled and oral corticosteroids repress systemic inflammation in chronic obstructive pulmonary disease (COPD). However, the cytokines that may respond to these medications are unclear.


METHODS
We used data from 41 patients with a history of stable moderate COPD (average age 64 years) who were randomised to inhaled fluticasone (500 microg twice daily from a Diskus inhaler), oral prednisone (30 mg daily) or placebo for 2 weeks. Using a multiplexed array system, different serum cytokines that have been implicated in COPD pathogenesis were measured.


RESULTS
We found that compared with placebo, inhaled fluticasone significantly reduced levels of soluble tumour necrosis factor receptor-2 (sTNF-R2) by 24% (95% CI, 7-38%; p = 0.01), monocyte chemoattractant protein-1 by 20% (95% CI, 5-32%; p = 0.01), interferon gamma inducible CXCL10 (IP-10) by 43% (95% CI, 3-66%; p = 0.04), and soluble L-selectin levels by 15% (95% CI, 1-28%; p = 0.04). Compared with placebo, oral prednisone reduced levels of sTNF-R2 by 26% (95% CI, 15-36%; p < 0.001), L-selectin by 22% (95% CI, 8-34%; p = 0.004), intercellular adhesion molecule-1 by 31% (95% CI, 9-48%; p = 0.01), pulmonary and activation-regulated chemokine (PARC) by 18% (95% CI, 2-32%; p = 0.03) and IP-10 by 40% (95% CI, 0-64%; p = 0.05). sTNF-R2, L-selectin and IP-10 were significantly reduced by both oral and inhaled corticosteroids. The other cytokines were not significantly repressed by either oral or inhaled corticosteroids.


CONCLUSIONS
In summary, inhaled and oral corticosteroids significantly repressed a selected number of systemic cytokines in patients with stable, moderate COPD; most of the steroid-responsive cytokines appear to be chemoattractants.
Man
S F Paul
SF
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Xuekui Zhang
Vessey
Rupert
R
Walker
Terry
T
Lee
Kwan
K
Park
Dan
D
Sin
Don D
DD
D000280:Administration, Inhalation; D000284:Administration, Oral; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy*
D000730:Androstadienes; D015415:Biomarkers; D016207:Cytokines; D005938:Glucocorticoids; D000068298:Fluticasone