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 th e lung, which may be suppressed with the help of exogenous anti-inflam matory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory trac t secretions. We report an inverse correlation between extracellular L C-1 concentration and the bronchoconstrictor prostaglandin (PG) D-2 [n = 15, Spearman rank correlation coefficient (r(s)) = -0.597, P < 0.05 ] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patie nts, together with positive correlations between extracellular LC-1 pe r milliliter BALF and the prostacyclin (PGI(2)) metabolite 6-keto-PGF( 1 alpha) (n = 15, r(s) = 0.80, P < 0.05) and between LC-1 per millilit er BALF and concentration of histamine causing a 20% decrease in force d expired volume in 1 s (n = 15, r(s) = 0.720, P < 0.01) in these subj ects. We found no significant difference between the LC-1 concentratio n in BALF from nonsmoking asthmatic patients who were receiving inhale d glucocorticoid therapy (2 x 100 mu g 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 nonsmoki ng counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumi n, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18 ; P < 0.05), perhaps because smokers' lungs contain more alveolar macr ophages, cells that release LC-1. We observed a positive correlation b etween BALF LC-1 and bronchoalveolar lavage cell number (n = 16, r(s) = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a pro tective response of the lung to inflammatory insult. Regulation of pro stanoid levels might be one mechanism by which LC-1 suppresses inflamm ation.