Eicosanoids and lipocortin-1 in bal-fluid in asthma: effects of
smoking and inhaled glucocorticoids.
Th., Peter, W. Van Hal, Shelley E. Overbeek, Henk C. Hoogsteden, Freek
J. Zijlstra, Kevin Murphy, Ytske Oosterhoff, Dirkje S. Postma, A.
Guz, and Susan F. Smith.
Departments of Immunology, Pulmonary Medicine and Pharmacology,
Erasmus University/University Hospital Dijkzigt, Rotterdam, The
Netherlands; Department of Medicine, Charing Cross and Westminster
Medical School, London, U.K.; Department of Pulmonary Medicine,
University Hospital Groningen, The Netherlands
APStracts 3:0138A, 1996.
Both smoking and asthma are associated with inflammatory changes in
the lung, which may be suppressed with the help of exogenous anti
-inflammatory drugs or by the endogenous defence system. Lipocortin-1
(Lc-1) is an anti-inflammatory protein present in respiratory tract
secretions. We report an inverse correlation between extracellular
Lc-1 concentration and the bronchoconstrictor prostaglandin D2 (PGD2)
(rs=-0.597, n=15, p<0.05) in bronchoalveolar lavage fluid (BALF)
from allergic asthmatics, together with positive correlations between
extracellular Lc-1/ml BALF and the prostacyclin (PGI2) metabolite, 6
-keto PGF1[alpha] (rs=0.480, n = 15, p < 0.05) and between Lc
-1/ml and PC20 (rs=0.720, n=15, p<0.01) in these subjects. We
found no significant difference between the Lc-1 concentration in
BALF from non-smoking asthmatic patients receiving inhaled
glucocorticoid therapy (2x100 [mu]g beclomethasone q.i.d. for 2.5 y;
median 186 ng Lc-1/mg albumin, n = 6) and those who were not (median
126 ng Lc-1/mg albumin, n = 12), perhaps because inhaled drugs
deposit predominantly in central airways which are poorly represented
in BAL. Both asthmatic and healthy volunteers who smoked had higher
levels of Lc-1 in their BALF than their non-smoking counterparts
(e.g. asthmatic smokers, median 317 ng Lc-1/mg albumin, n=10;
asthmatic non-smokers, median 162 ng Lc-1/mg albumin, n=18;
p<0.05), perhaps because smokers' lungs contain more alveolar
macrophages, cells which release Lc-1. We observed a positive
correlation between BALF Lc-1 and BAL cell number (rs=0.821, n=16,
p<0.001). Increased extracellular Lc-1 may be part of a
protective response of the lung to inflammatory insult. Regulation of
prostanoid levels might be one mechanism by which Lc-1 suppresses
inflammation.
Received 4 August 1995; accepted in final form 26 February 1996.
APS Manuscript Number A859-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96