In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion.
Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.
Llewellyn-Jones
C G
CG
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, UK.
Johnson
M M
MM
Mitchell
J L
JL
Pye
A
A
Okafor
V C
VC
Hill
S L
SL
Stockley
R A
RA
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001987:Bronchiectasis / Q000188:drug therapy* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D005353:Fibronectins / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013183:Sputum / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D013482:Superoxide Dismutase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005353:Fibronectins; D009195:Peroxidase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D007213:Indomethacin