Bronchial challenge with adenosine causes the release of serum neutrophil chemotactic factor in asthma.
In order to investigate the mechanism of adenosine-induced bronchoconstriction in asthma, serum neutrophil chemotactic activity (NCA) was measured in normal individuals and patients with asthma before and 5 min after bronchoprovocation testing with adenosine. Challenge testing was terminated when the FEV1 fell by 20% or a concentration of 10 mg/ml was reached. Participants were separated into three groups: six asthmatics hyperresponsive to adenosine (Group 1), seven asthmatics hyperresponsive to histamine but not adenosine (Group 2), and six normal subjects (Group 3). The mean percentage increase in NCA was 84% for Group 1 (p less than 0.001), 29% for Group 2 (p less than 0.05), and only 13% for Group 3. No significant increase in NCA was observed after histamine challenge in seven individuals with asthma derived from Groups 1 and 2. Four patients from Group 1 were rechallenged after treatment with therapeutic doses of oral theophylline. Theophylline therapy was associated with a significant attenuation of the increase in NCA at the concentration of adenosine which caused a 20% decrease in FEV1 before treatment (18% versus 84%, p less than 0.01). The concentration of adenosine which caused a 20% drop in FEV1 was increased at least twofold for each of the four patients. Analysis of NCA by gel filtration chromatography demonstrated an increase in a high molecular weight neutrophil chemotactic factor in the serum of two Group 1 patients after adenosine challenge. Release of a high molecular weight neutrophil chemotactic factor is consistent with a mast cell source for inflammatory mediators in adenosine-induced bronchoconstriction. The therapeutic effects of theophylline, a potent adenosine antagonist, in asthma may therefore occur in part through the inhibition of this process.
Driver
A G
AG
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.
Kukoly
C A
CA
Metzger
W J
WJ
Mustafa
S J
SJ
D000241:Adenosine; D000328:Adult; D001249:Asthma / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D013806:Theophylline / Q000627:therapeutic use
D016209:Interleukin-8; D013806:Theophylline; D000241:Adenosine