Leukotrienes and isocyanate-induced asthma: a pilot study.
BACKGROUND
The role of leukotrienes (LTs) in the pathophysiology of isocyanate-induced asthma is not well known.


OBJECTIVE
We sought to characterize the type of airway inflammation induced by exposure to isocyanates and to investigate whether exposure to isocyanates induced an increase in LT receptor cysteinyl leukotriene ((CysLT)(1), CysLT(2) and leukotriene B(4) receptor (BLT(1))) expression, as well as a release of LT (LTC(4) and leukotriene B(4) (LTB(4))) and IL-8 in both asthmatics with isocyanate-induced asthma and healthy subjects.


METHODS
We investigated eight subjects with isocyanate-induced asthma and eight healthy subjects. Both groups underwent specific inhalation challenges to isocyanates in the laboratory. Induced sputum was collected before and after exposure to isocyanates. CysLT(1), CysLT(2) and BLT(1) expression was assessed by flow cytometry, whereas LTC(4), LTB(4) and IL-8 were measured in the sputum supernatants by enzyme immunoassay.


RESULTS
Exposure to isocyanates induced an increase in sputum neutrophils only in subjects with occupational asthma. There was a significant increase in CysLT(1) and BLT(1) receptor expression, as well as a release of LTB(4) and IL-8 after exposure to isocyanates compared with the baseline, only in subjects with isocyanate-induced asthma, whereas there was no increase in LTC(4). Exposure to isocyanates did not induce any change in LT receptor expression nor in the levels of LTC(4), LTB(4) and IL-8, in healthy subjects.


CONCLUSIONS
The neutrophilia observed after exposure to isocyanates is likely to be related to the release of LTB(4), probably enhanced by the increased expression of BLT(1) on neutrophils as well as by the release of IL-8. The significance of the increase of CysLT1 receptor expression on neutrophils is unknown and needs further investigation.
Lemiere
C
C
Department of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, University of Montreal, QC, Canada. lemierec@crhsc.umontreal.ca
Pelissier
S
S
Tremblay
C
C
Chaboillez
S
S
Thivierge
M
M
Stankova
J
J
Rola-Pleszczynski
M
M
D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D003545:Cysteine / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8; D017953:Isocyanates / Q000633:toxicity*; D015289:Leukotrienes / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D009784:Occupational Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010865:Pilot Projects; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2 / Q000097:blood / Q000378:metabolism; D013183:Sputum / Q000166:cytology / Q000378:metabolism
D016209:Interleukin-8; D017953:Isocyanates; C513240:LTB4R protein, human; D015289:Leukotrienes; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; C112381:cysteinyl-leukotriene; D003545:Cysteine