Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids.
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 defense system. Lipocortin-1 (LC-1; annexin-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 (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; 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 bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, 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.
Van Hal
P T
PT
Department of Medicine, Charing Cross and Westminster Medical School, London, United Kingdom.
Overbeek
S E
SE
Hoogsteden
H C
HC
Zijlstra
F J
FJ
Murphy
K
K
Oosterhoff
Y
Y
Postma
D S
DS
Guz
A
A
Smith
S F
SF
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000280:Administration, Inhalation; D000328:Adult; D017305:Annexin A1 / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015777:Eicosanoids / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012129:Respiratory Function Tests; D012907:Smoking / Q000378:metabolism*
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D015777:Eicosanoids; D005938:Glucocorticoids; D015121:6-Ketoprostaglandin F1 alpha; D006632:Histamine; D001507:Beclomethasone