Increased activity of interleukin-6 but not tumor necrosis factor-alpha in lung lavage of premature infants is associated with the development of bronchopulmonary dysplasia.
Although considerable evidence suggests that bronchopulmonary dysplasia (BPD) is the result of prolonged inflammation and impaired healing of the immature lung, the mediators that regulate inflammation in neonatal lung injury have not been completely elucidated. We examined whether the cytokines IL-6 and tumor necrosis factor-alpha (TNF) interact to modulate a cascade of cell-cell signaling events involved in inflammation contributing to the development of BPD. To determine the relative activities of these cytokines in neonatal lung injury, lung lavage samples were serially obtained from 1 to 28 d from 11 infants with self-limited respiratory distress syndrome (RDS), 19 infants with evolving BPD, and 10 control infants ventilated for nonpulmonary reasons. On the first day of life, there were no differences in antigenic IL-6 concentrations in lavage fluids among the BPD, RDS, and control groups, but IL-6 activity determined by the 7TD1 proliferation assay was 15-fold and 6.6-fold higher in lung lavage of infants who developed BPD compared with activities in lavage from control and RDS infants, respectively (control, 49.4 +/- 17.6; RDS, 117.3 +/- 59.6; BPD, 779.5 +/- 212.6 x 10(3) hybridoma units/L, mean +/- SEM, p = 0.02). This suggests that pathways for inactivating or inhibiting IL-6 that may be present in the lungs of RDS and control infants may be deficient in BPD infants. IL-6 activity remained elevated in lavage of BPD infants for the first 2 wk and declined to low levels by d 28.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201.
A
A
Bagchi
R M
RM
Viscardi
V
V
Taciak
J E
JE
Ensor
K A
KA
McCrea
J D
JD
Hasday
D000367:Age Factors; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000276:immunology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications / Q000276:immunology; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha