Impact of Histological Chorioamnionitis on Tracheal Aspirate Cytokines in Premature Infants

Abstract

Background Histological chorioamnionitis (CHORIO) may increase inflammatory mediators in the lungs of preterm infants.

Objective To study the impact of CHORIO on tracheal aspirate (TA) cytokines in ventilated infants.

Design/Methods TA samples collected within 48 hours after birth from 40 ventilated neonates (gestational age [GA] <30 weeks, body weight [BW] <1250 g) were analyzed. Levels of 12 cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, epidermal growth factor [EGF], interferon-γ [IFN-γ], monocyte chemotactic protein-1 [MCP-1], tumor necrosis factor-α [TNF-α], vascular endothelial growth factor [VEGF]) were measured using a biochip multianalyte immunoassay (Randox Laboratories, Antrim, UK). Total protein was measured by the Bradford assay. CHORIO assessment was done by a blinded pathologist.

Results Twenty-six infants (GA 26.6 ± 1.4 weeks, BW 852 ± 162 g) had no CHORIO and 14 (GA 25.1 ± 1.0 weeks, BW 776 ± 164 g) had CHORIO. IL-1α, IL-1β, IL-8, and VEGF were significantly higher in TA of infants with CHORIO. After correction for dilution, IL-1α, IL-1β, and IL-8 were significantly elevated. Increased TA total cell count correlated with CHORIO, VEGF, EGF, MCP-1, IL-8, and IL-6 TA levels (all p ≤ 0.02). Ventilator, oxygen supplementation, and hospital days correlated with TA IFN-γ levels (all p ≤ 0.01).

Conclusion CHORIO is associated with increased specific proinflammatory mediators in TA samples of preterm infants.

Keywords

inflammatory mediators - placenta - neonate - lung

• References

• 1 Buhimschi CS, Dulay AT, Abdel-Razeq S , et al. Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth. BJOG 2009; 116: 257-267
• 2 Romero R, Espinoza J, Gonçalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007; 25: 21-39
• 3 Buhimschi CS, Baumbusch MA, Dulay AT , et al. Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury. Am J Pathol 2009; 175: 958-975
• 4 Buhimschi CS, Buhimschi IA, Abdel-Razeq S , et al. Proteomic biomarkers of intra-amniotic inflammation: relationship with funisitis and early-onset sepsis in the premature neonate. Pediatr Res 2007; 61: 318-324
• 5 Bracci R, Buonocore G. Chorioamnionitis: a risk factor for fetal and neonatal morbidity. Biol Neonate 2003; 83: 85-96
• 6 Hagberg H, Wennerholm UB, Sävman K. Sequelae of chorioamnionitis. Curr Opin Infect Dis 2002; 15: 301-306
• 7 Thompson A, Bhandari V. Pulmonary biomarkers of bronchopulmonary dysplasia. Biomark Insights 2008; 3: 361-373
• 8 Bhandari A, Bhandari V. Pitfalls, problems, and progress in bronchopulmonary dysplasia. Pediatrics 2009; 123: 1562-1573
• 9 Munshi UK, Niu JO, Siddiq MM, Parton LA. Elevation of interleukin-8 and interleukin-6 precedes the influx of neutrophils in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia. Pediatr Pulmonol 1997; 24: 331-336
• 10 Kakkera DK, Siddiq MM, Parton LA. Interleukin-1 balance in the lungs of preterm infants who develop bronchopulmonary dysplasia. Biol Neonate 2005; 87: 82-90
• 11 De Dooy J, Colpaert C, Schuerwegh A , et al. Relationship between histologic chorioamnionitis and early inflammatory variables in blood, tracheal aspirates, and endotracheal colonization in preterm infants. Pediatr Res 2003; 54: 113-119
• 12 Ambalavanan N, Novak ZE. Peptide growth factors in tracheal aspirates of mechanically ventilated preterm neonates. Pediatr Res 2003; 53: 240-244
• 13 Cayabyab RG, Jones CA, Kwong KY , et al. Interleukin-1beta in the bronchoalveolar lavage fluid of premature neonates: a marker for maternal chorioamnionitis and predictor of adverse neonatal outcome. J Matern Fetal Neonatal Med 2003; 14: 205-211
• 14 Baier RJ, Majid A, Parupia H, Loggins J, Kruger TE. CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia. Pediatr Pulmonol 2004; 37: 137-148
• 15 Cheah FC, Winterbourn CC, Darlow BA, Mocatta TJ, Vissers MC. Nuclear factor kappaB activation in pulmonary leukocytes from infants with hyaline membrane disease: associations with chorioamnionitis and Ureaplasma urealyticum colonization. Pediatr Res 2005; 57 (5 Pt 1) 616-623
• 16 Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C ; Society for Pediatric Pathology, Perinatal Section, Amniotic Fluid Infection Nosology Committee. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2003; 6: 435-448
• 17 Fitzgerald SP, McConnell RI, Huxley A. Simultaneous analysis of circulating human cytokines using a high-sensitivity cytokine biochip array. J Proteome Res 2008; 7: 450-455
• 18 Aghai ZH, Faqiri S, Saslow JG , et al. Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone. J Perinatol 2008; 28: 149-155
• 19 Lassus P, Ristimäki A, Ylikorkala O, Viinikka L, Andersson S. Vascular endothelial growth factor in human preterm lung. Am J Respir Crit Care Med 1999; 159 (5 Pt 1) 1429-1433
• 20 Arai H, Matsuda T, Goto R, Takada G. Increased numbers of macrophages in tracheal aspirates in premature infants with funisitis. Pediatr Int 2008; 50: 184-188
• 21 Thomas W, Seidenspinner S, Kawczyńska-Leda N , et al. Clara cell secretory protein in tracheobronchial aspirates and umbilical cord serum of extremely premature infants with systemic inflammation. Neonatology 2010; 97: 228-234