The TNF-alpha -308, MCP-1 -2518 and TGF-beta1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants.

Chronic lung disease (CLD) in premature newborns is associated with increased concentrations of inflammatory cytokines in tracheal aspirates (TA). We determined if polymorphisms of cytokine genes influence the risk of developing CLD by genotyping 178 mechanically ventilated very low birth weight (VLBW) infants for the tumor necrosis factor-alpha (TNF-alpha) -308 G/A, transforming growth factor-beta(1) (TGF-beta(1)) +915 G/C and monocyte chemoattractant protein-1 (MCP-1) -2518 A/G polymorphisms. Genomic DNA was isolated from TA and genotypes determined by restriction length polymorphism. There was no effect of any of these polymorphisms on the development of CLD (29 vs 23%, P=0.371, TNF-alpha -308 AA/AG vs TNF-alpha -308 GG; 23 vs 26%, P=0.681, MCP-1 -2518 GG/AG vs MCP-1 -215-8 AA; 24 vs 24%, P=0.978, TGF-beta(1) +915 CG vs TGF-beta(1) +915 GG). TA IL-8 and MCP-1 concentrations were not different between genotype groups. Infants with the TNF-alpha -308 A allele had increased risk of IVH (RR 2.07; 95% CI 1.02-4.18, P=0.041) and infants with the TGF-beta(1) +915 C allele were at greater risk of death (32 vs 9%, P=0.016). These data suggest that these polymorphisms do not play a significant role in determining risk for CLD in preterm infants, but may play a role in other complications in the neonatal period.

Monocyte chemoattractant protein-1 and interleukin-8 are increased in bronchopulmonary dysplasia: relation to isolation of Ureaplasma urealyticum.

BACKGROUND: An exaggerated inflammatory response occurs in infants who subsequently develop bronchopulmonary dysplasia (BPD). Ureaplasma urealyticum (Uu) is frequently isolated from cultures of tracheal secretions obtained from very low birth weight infants and is associated with an increased risk of BPD. METHODS: We examined the relationships between isolation of genital mycoplasmas, tracheal aspirate (TA) interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) concentrations and the development of BPD. Serial TAs were obtained prospectively from 35 very low birth weight infants, and IL-8 and MCP-1 concentrations were determined by enzyme-linked immunoadsorbent assay. Tracheal cultures for bacteria and genital mycoplasmas were performed on aspirates obtained during the first 2 days of life. RESULTS: Infants who developed BPD (n=18) were less mature (25.2+/-0.2 vs 27.8+/-0.5 weeks; P<0.001), of lower birth weight (746+/-28 vs 1052+/-41 g; P<0.001), and more likely to have a positive tracheal culture for Uu (39% vs 6%; P=0.026) than those who did not develop BPD (n=17). Tracheal concentrations of IL-8 and MCP-1 were significantly increased in infants who developed BPD (IL-8: P=0.0001; MCP-1: P<0.001, analysis of variance) and correlated with duration of mechanical ventilation and oxygen treatment. Uu-positive infants had an increased incidence of BPD (88% in infants with Uu vs 42% in infants without Uu; P=0.020) and had TA concentrations of IL-8 and MCP-1 that were significantly increased compared with those of Uu-negative infants. CONCLUSIONS: Increased TA concentrations of IL-8 and MCP-1 during the first 2 weeks of life are associated with the development of BPD. Recovery of Uu from TAs is associated with a more robust inflammatory reaction and an increased risk of BPD.