LEVELS OF COMPLEMENT ANAPHYLATOXIN C5A IN PULMONARY EFFLUENT FLUID OFINFANTS AT RISK FOR CHRONIC LUNG-DISEASE AND EFFECTS OF DEXAMETHASONETREATMENT

A number of studies have shown that increased numbers of neutrophils a nd macrophages are recruited into the airways during the development o f chronic lung disease (CLD) in preterm infants. The objective of this study was to determine whether the anaphylatoxin C5a is detectable in tracheobronchial aspirate fluid of infants at risk for CLD and to eva luate the possible effects of dexamethasone (Dxm) treatment. C5a/C5a(d es Arg) levels were determined by a sensitive ELISA based on a neoepit ope-specific MAb. In a prospective study, 27 infants (birth weight 881 +/- 169 g, mean /- SD) still on mechanical ventilation at d 10 postna tal age with fraction of inspired oxygen greater than or equal to 0.3 and/or peak inspiratory pressure greater than or equal to 16 cm H2O we re randomly assigned to Dxm treatment at d 10 (n = 14) or d 16 (n = 13 ). Ten mechanically ventilated infants with no respiratory disease or who had recovered from respiratory distress syndrome did not meet thes e criteria on d 10 and served as a control group (birth weight 928 +/- 126 g). For the evaluation of Dxm therapy, the late treatment group w as used as a control group for the early regimen. Compared with contro ls, C5a concentrations were higher in infants at risk for CLD on d 10 [median (25th-75th percentile): 2.40 (1.13-3.38) versus 0.82 (0.55-1.7 8) mu g/L, p < 0.05]. After Dxm, C5a concentrations decreased signific antly in the early treatment group compared with pretreatment values i n the late treatment group [d 15, pre Dxm 2.22 (0.98-3.92), post Dxm 0 .57 (0.18-1.02) mu g/L, p < 0.01]. C5a levels in plasma of eight infan ts were not affected by Dxm treatment. Our results show that increased levels of complement anaphylatoxin C5a are present in lung effluent f luid of infants at risk for CLD, and that local but not systemic level s are affected by Dxm. These findings indicate a role of C5a in the re cruitment of inflammatory cells into the airways of infants with CLD.