ABSTRACT
We examined the effect of dexamethasone on the expression of the adhesion molecule L-selectin on circulating polymorphonuclear leukocytes (PMLs) and monocytes from premature infants with bronchopulmonary dysplasia (BPD). Nineteen infants who received dexamethasone (Dex group) and 28 who did not receive dexamethasone (no Dex group) were studied. L-selectin expression, measured as mean fluorescence intensity, was lower on circulating PMLs (5.7 +/- 0.6 vs 10.6 +/- 0.7, p < 0.001) and monocytes (7.9 +/- 0.9 vs 12.5 +/- 0.9, p < 0.02) isolated from those who had received dexamethasone. Because L-selectin is important for the recruitment of PMLs to inflammatory foci in the lungs, we speculate that one of the mechanisms by which dexamethasone reduces inflammation in BPD is by impairing the ability of leukocytes to migrate into the BPD lesions.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Bronchopulmonary Dysplasia/drug therapy , Bronchopulmonary Dysplasia/immunology , Dexamethasone/pharmacology , L-Selectin/analysis , Leukocytes, Mononuclear/immunology , Anti-Inflammatory Agents/therapeutic use , CD18 Antigens/analysis , Dexamethasone/therapeutic use , Flow Cytometry , Humans , Infant, Newborn , Infant, Premature , L-Selectin/biosynthesis , Leukocytes, Mononuclear/drug effects , Monocytes/drug effects , Monocytes/immunologyABSTRACT
OBJECTIVE: To investigate secretory leukocyte protease inhibitor (SLPI) concentrations in tracheal lavage fluids of neonates with an endotracheal tube in place during the first month of life, and to evaluate the relationship of SLPI to neutrophil counts and elastase activity in patients in whom bronchopulmonary dysplasia (BPD) developed versus those in whom it did not. DESIGN: A prospective, inception cohort study. SETTING: University children's hospital neonatal intensive care unit. PATIENTS: Fifty-three neonates who weighed < 2000 gm at birth, and who had an endotracheal tube in place, were enrolled. Forth-one patients survived to 28 days; BPD developed in 24 but not in 17 patients. MAIN OUTCOME MEASURES: Tracheal lavage was performed on days 1, 2, 4, 7, 14, 21, and 28, and analyzed for neutrophils, elastase activity, and SLPI. Results were evaluated longitudinally for 28 days, and were compared between BPD and no-BPD groups during the first week. RESULTS: SLPI concentrations increased significantly for all patients during the study period. During the first week, SLPI concentrations were similar between BPD and no-BPD groups; neutrophil counts and elastase activity were higher in the BPD group. CONCLUSIONS: Patients in whom BPD ultimately developed had early evidence of increased pulmonary inflammation and a significantly less favorable protease-antiprotease balance. If elastase-induced injury contributes to the development of BPD, early therapy with recombinant SLPI might be beneficial by increasing the antielastase capacity of epithelial lining fluid.