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.
MerrittTA, StuardID, PucciaJ, WoodB, EdwardsDK, FinkelsteinJ, ShapiroDL.Newborn tracheal aspirate cytology: Classification during respiratory distress syndrome and bronchopulmonary dysplasia. J Pediatr1981;98:949–956.
2.
RindfleischMS, HasdayJD, TaciakV, BroderickK, ViscardiRM.Potential role of interleukin-1 in the development of bronchopulmonary dysplasia. J Interferon Cytokine Res1996;16:365–373.
3.
OgdenBE, MurphyS, SaundersGC, JohnsonJD.Lung lavage of newborns with respiratory distress syndrome. Prolonged neutrophil influx is associated with bronchopulmonary dysplasia. Chest1983;8331S-33S.
4.
GroneckP, Götze-SpeerB, OppermannM, EiffertH, SpeerCP.Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: A sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics1994;93:712–718.
5.
JonssonB, TullusK, BraunerA, LuY, NoackG.Early increase of TNF alpha and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed1997;77:198–201.
6.
MurchSH, CosteloeK, KleinNJ, MacDonaldTT.Early production of macrophage inflammatory protein-1 alpha occurs in respiratory distress syndrome and is associated with poor outcome. Pediatr Res1996;40:490–497.
7.
TullusK, NoackGW, BurmanLG, NilssonR, WretlindB, BraunerA.Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasia. Eur J Pediatr1996;155:112–116.
8.
KotechaS, WilsonL, WangooA, SilvermanM, ShawRJ.Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. Pediatr Res1996;40:250–256.
9.
KotechaS, ChanB, AzamN, SilvermanM, ShawRJ.Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease. Arch Dis Child Fetal Neonatal Ed1995;72:F90–F96.
10.
WatterbergKL, DemersLM, ScottSM, MurphyS.Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics1996;97:210–215.
11.
MunshiUK, NiuJO, SiddiqMM, PartonLA.Elevation of interleukin-8 and interleukin-6 precedes the influx of neutrophils in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia. Pediatr Pulmonol1997;24:331–336.
12.
MukaidaN, HaradaA, MatsushimaK.Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine Growth Factor Rev1998;9:9–23.
13.
ZhangK, PhanSH.Cytokines and pulmonary fibrosis. Biol Signals1996;5:232–239.
14.
SmithRE, StrieterRM, ZhangK, PhanSH, StandifordTJ, LukacsNW, KunkelSL.A role for C-C chemokines in fibrotic lung disease. J Leukoc Biol1995;57:782–787.
15.
VaillantP, MenardO, VignaudJM, MartinetN, MartinetY.The role of cytokines in human lung fibrosis. Monaldi Arch Chest Dis1996;51:145–152.
16.
SmithRE, StrieterRM, PhanSH, KunkelSL.C-C chemokines. Novel mediators of the profibrotic inflammatory response to bleomycin challenge. Am J Respir Cell Mol Biol1996;15:693–702.
17.
CarBD, MeloniF, LuisettiM, SemenzatoG, Gialdroni-GrassiG, WalzA.Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med1994;149:655–659.
18.
StandifordTJ, HuffnagleGB.Cytokines in host defense against pneumonia. J Investig Med1997;45:335–345.
19.
CassellGH, WaitesKB, CrouseDT, RuddPT, CanuppKC, StagnoS, CutterGR.Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birth-weight infants. Lancet1988;2:240–245.
20.
WangEE, FrayhaH, WattsJ, HammerbergO, CherneskyMA, MahonyJB, CassellGH.Role of Ureaplasma urealyticum and other pathogens in the development of chronic lung disease of prematurity. Pediatr Infect Dis J1998;7:547–551.
21.
WangEE, OhlssonA, KellnerJD.Association of Ureaplasma urealyticum colonization with chronic lung disease of prematurity: Results of a metaanalysis. J Pediatr1995;127:640–644.
22.
GroneckP, Goetze-SpeerB, SpeerCP.Inflammatory bronchopulmonary response of preterm infants with microbial colonization of the airways at birth. Arch Dis Child Fetal Neonatal Ed1996;74:F51–F55.
23.
PattersonAM, TaciakV, LovchikJ, FoxRE, CampbellAB, ViscardiRM.Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin 6 in tracheal aspirates of preterm infants. Pediatr Infect Dis J1998;17:321–328.
24.
PaltaM, SadekM, BarnetJH, EvansM, WeinsteinMR, McGuinnessG, PetersME, GabbertD, FrybackD, FarrellP.Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. J Pediatr1998;132:57–63.
25.
IsenbergHD. ed. Clinical Microbiology Procedures Handbook. Washington, DC: American Society for Microbiology; 1994.
26.
WattsCL, BruceMC.Comparison of secretory component for immunoglobulin A with albumin as reference proteins in tracheal aspirate from preterm infants. J Pediatr1995;127:113–122.
27.
GoodmanRB, StrieterRM, MartinDP, SteinbergKP, MilbergJA, MaunderRJ, KunkelSL, WalzA, HudsonLD, MartinTR.Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med1996;154:602–611.
28.
TemelkovskiJ, KumarRK, MaroneseSE.Enhanced production of an EGF-like growth factor by parenchymal macrophages following bleomycin-induced pulmonary injury. Exp Lung Res1997;23:377–391.
29.
MaedaA, HiyamaK, YamakidoH, IshiokaS, YamakidoM.Increased expression of platelet-derived growth factor A and insulin-like growth factor-I in BAL cells during the development of bleomycin-induced pulmonary fibrosis in mice. Chest1996;109:780–786.
30.
Gharaee-KermaniM, DenholmEM, PhanSH.Costimulation of fibroblast collagen and transforming growth factor beta1 gene expression by monocyte chemoattractant protein-1 via specific receptors. J Biol Chem1996;271:17779–17784.
31.
LyonAJ, McColmJ, MiddlemistL, FergussonS, McIntoshN, RossPW.Randomised trial of erythromycin on the development of chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed1998;78:F10–F14.
32.
StancombeBB, WalshWF, DerdakS, DixonP, HensleyD.Induction of human neonatal pulmonary fibroblast cytokines by hyperoxia and Ureaplasma urealyticum. Clin Infect Dis1993;17(suppl 1):S154–S157.
33.
CrouseDT, EnglishBK, LivingstonL, MealsEA.Genital mycoplasmas stimulate tumor necrosis factor-alpha and inducible nitric oxide synthase production from a murine macrophage cell line. Pediatr Res1998;4:785–790.
BaierRJ, KrugerTE.Induction of monocyte chemoattractant protein-1 by Mycoplasma hominis in respiratory epithelial cells. J Investig Med2000;48:457–464.
36.
KrugerT, BaierJ.Induction of neutrophil chemoattractant cytokines by Mycoplasma hominis in alveolar type II cells. Infect Immun1997;65:5131–5136.
