Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids.
The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in airway epithelial cells in vivo was assessed in 15 asthmatic and 9 normal subjects. GM-CSF was analyzed using immunohistochemistry with a polyclonal and a monoclonal antibody. Hue saturation intensity color image analysis was used to quantify staining. Asthmatic airway epithelial cells stained significantly more with anti-GM-CSF than those from normal subjects (p = 0.0013 and p = 0.0003 for the polyclonal and monoclonal antibodies, respectively). Additionally, 8 asthmatic individuals inhaled 1,000 micrograms beclomethasone diproprionate per day for 8 wk and 6 asthmatic patients inhaled matching placebo. There was a significant reduction of GM-CSF in the epithelium in the patients who were given corticosteroids (p = 0.014), whereas the group of subjects who were given placebo showed no significant change in GM-CSF staining. There was a correlation between the percentage suppression of GM-CSF staining by inhaled corticosteroids and the percentage increase in FEV1 (r = 0.61, p < 0.05) and percentage decrease in carbachol responsiveness (r = 0.80, p < 0.01). These findings suggest that GM-CSF may play a role in the inflammatory processes of bronchial asthma and that the epithelial cell may be a target cell for drug action.
Department of Experimental Pathology, United Medical School, Guy's Hospital, London, United Kingdom.
A R
AR
Sousa
R N
RN
Poston
S J
SJ
Lane
J A
JA
Nakhosteen
T H
TH
Lee
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001507:Beclomethasone / Q000008:administration & dosage*; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001999:Bronchoscopy; D002217:Carbachol / Q000494:pharmacology; D004311:Double-Blind Method; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002217:Carbachol; D001507:Beclomethasone