Skip to main content
SpringerLink
Log in

Prenatal and Postnatal Inflammatory Mechanisms

  • Reference work entry
  • First Online:
Neonatology

  • 193 Accesses

Abstract

During the past 20 years, intrauterine infection and inflammation have been identified as significant risk factors in the development of fetal and neonatal morbidity and mortality, as well as adverse long-term outcome in very immature preterm infants. Besides severe infections, immature preterm infants are at high risk for syndromes of dysregulated inflammation including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and preterm cerebral white matter disease (WMD). Although pathogenesis is multifactorial, inflammation has been acknowledged as principle mechanism, being caused, sustained, and aggravated by multiple perinatal factors interacting in a multiple-hit sequence. An inflammatory state is presumed to be either initiated prenatally by chorioamnionitis or induced and sustained by pro-inflammatory postnatal conditions, such as oxygen toxicity, mechanical ventilation, and neonatal infection. Perturbation of pro- and anti-inflammatory central signaling pathways and subsequently imbalanced inflammatory responses may lead to severe organ injury affecting parenchymal development during a window of vulnerability. Maturation-dependent factors and genetic predisposition may underlie a particular vulnerability.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 479.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 799.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BALF:

Bronchoalveolar lavage fluid

BPD:

Bronchopulmonary dysplasia

CA:

Chorioamnionitis

CP:

Cerebral palsy

CPAP:

Continuous positive airway pressure

CSF:

Cerebrospinal fluid

ELBW:

Extremely low birth weight

EOS:

Early-onset sepsis

FIRS:

Fetal inflammatory response syndrome

ICAM:

Intercellular adhesion molecules

IFN-γ:

Interferon-y

IL:

Interleukin

IL-1ra:

IL-1 receptor antagonist

IRAK:

IL-1 receptor-associated kinase

LOS:

Late-onset sepsis

LPS:

Lipopolysaccharide (endotoxin)

MCP:

Monocyte chemoattractant protein

MIP:

Macrophage inflammatory protein

MMP:

Matrix metalloproteinase

MRI:

Magnetic resonance imaging

NF-KB:

Nuclear transcription factor KB

PCR:

Polymerase chain reaction

PMNs:

Polymorphonuclear cells

Pre-OLs:

Pre-myelinating oligodendrocytes

PRR:

Pattern recognition receptor

RDS:

Respiratory distress syndrome

ROS:

Reactive oxygen species

SP:

Surfactant protein

TGF-β:

Transforming growth factor-β

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

VCAM:

Vascular cell adhesion molecules

VEGF:

Vascular endothelial growth factor

References

  • Adams EW, Harrison MC, Counsell SJ, Allsop JM, Kennea NL, Hajnal JV et al (2004) Increased lung water and tissue damage in bronchopulmonary dysplasia. J Pediatr 145:503–507

    Article  PubMed  Google Scholar 

  • Akira S (2006) TLR signaling. Curr Top Microbiol Immunol 311:1–16

    CAS  PubMed  Google Scholar 

  • Altiok O, Yasumatsu R, Bingol-Karakoc G, Riese RJ, Stahlman MT, Dwyer W et al (2006) Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia. Am J Respir Crit Care Med 173:318–326

    Article  CAS  PubMed  Google Scholar 

  • Backstrom E, Hogmalm A, Lappalainen U, Bry K (2011) Developmental stage is a major determinant of lung injury in a murine model of bronchopulmonary dysplasia. Pediatr Res 69:312–318

    Article  PubMed  Google Scholar 

  • Baier RJ, Majid A, Parupia H, Loggins J, Kruger TE (2004) CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia. Pediatr Pulmonol 37:137–148

    Article  PubMed  Google Scholar 

  • Barton SK, Moss TJ, Hooper SB, Crossley KJ, Gill AW, Kluckow M et al (2014) Protective ventilation of preterm lambs exposed to acute chorioamnionitis does not reduce ventilation-induced lung or brain injury. PLoS One 9:e112402

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bartram U, Speer CP (2004) The role of transforming growth factor beta in lung development and disease. Chest 125:754–765

    Article  PubMed  Google Scholar 

  • Benjamin JT, Smith RJ, Halloran BA, Day TJ, Kelly DR, Prince LS (2007) FGF-10 is decreased in bronchopulmonary dysplasia and suppressed by Toll-like receptor activation. Am J Physiol Lung Cell Mol Physiol 292:L550–L558

    Article  CAS  PubMed  Google Scholar 

  • Berger I, Peleg O, Ofek-Shlomai N (2012) Inflammation and early brain injury in term and preterm infants. Isr Med Assoc J 14:318–323

    PubMed  Google Scholar 

  • Bersani I, Speer CP (2012) Nosocomial sepsis in neonatal intensive care: inevitable or preventable? Z Geburtshilfe Neonatol 216:186–190

    Article  CAS  PubMed  Google Scholar 

  • Bersani I, Kunzmann S, Speer CP (2013) Immunomodulatory properties of surfactant preparations. Expert Rev Anti Infect Ther 11:99–110

    Article  CAS  PubMed  Google Scholar 

  • Bhandari V (2010) Hyperoxia-derived lung damage in preterm infants. Semin Fetal Neonatal Med 15:223–229

    Article  PubMed  PubMed Central  Google Scholar 

  • Bhandari V, Elias JA (2006) Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. Free Radic Biol Med 41:4–18

    Article  CAS  PubMed  Google Scholar 

  • Blackwell TS, Hipps AN, Yamamoto Y, Han W, Barham WJ, Ostrowski MC et al (2011) NF-kappaB signaling in fetal lung macrophages disrupts airway morphogenesis. J Immunol 187:2740–2747

    Article  CAS  PubMed  Google Scholar 

  • Boghossian NS, Page GP, Bell EF, Stoll BJ, Murray JC, Cotten CM et al (2013) Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr 162:1120–1124, 1124 e1121

    Article  PubMed  PubMed Central  Google Scholar 

  • Bose CL, Dammann CE, Laughon MM (2008) Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate. Arch Dis Child Fetal Neonatal Ed 93:F455–F461

    Article  CAS  PubMed  Google Scholar 

  • Bose CL, Laughon MM, Allred EN, O’Shea TM, Van Marter LJ, Ehrenkranz RA et al (2013) Systemic inflammation associated with mechanical ventilation among extremely preterm infants. Cytokine 61:315–322

    Article  CAS  PubMed  Google Scholar 

  • Brehmer F, Bendix I, Prager S, van de Looij Y, Reinboth BS, Zimmermanns J et al (2012) Interaction of inflammation and hyperoxia in a rat model of neonatal white matter damage. PLoS One 7:e49023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brew N, Hooper SB, Allison BJ, Wallace MJ, Harding R (2011) Injury and repair in the very immature lung following brief mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 301:L917–L926

    Article  CAS  PubMed  Google Scholar 

  • Brochu ME, Girard S, Lavoie K, Sebire G (2011) Developmental regulation of the neuroinflammatory responses to LPS and/or hypoxia-ischemia between preterm and term neonates: an experimental study. J Neuroinflammation 8:55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai Z, Pang Y, Lin S, Rhodes PG (2003) Differential roles of tumor necrosis factor-alpha and interleukin-1 beta in lipopolysaccharide-induced brain injury in the neonatal rat. Brain Res 975:37–47

    Article  CAS  PubMed  Google Scholar 

  • Cederqvist K, Sorsa T, Tervahartiala T, Maisi P, Reunanen K, Lassus P et al (2001) Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 108:686–692

    Article  CAS  PubMed  Google Scholar 

  • Chetty A, Cao GJ, Severgnini M, Simon A, Warburton R, Nielsen HC (2008) Role of matrix metalloprotease-9 in hyperoxic injury in developing lung. Am J Physiol Lung Cell Mol Physiol 295:L584–L592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chew LJ, DeBoy CA (2015) Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology. Neurol. pii: S0028-3908(15)00266-X. https://doi.org/10.1016/j.neuropharm.2015.06.008. [Epub ahead of print]

    Article  CAS  PubMed  Google Scholar 

  • Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C et al (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243–1249

    Article  CAS  PubMed  Google Scholar 

  • D’Alquen D, Kramer BW, Seidenspinner S, Marx A, Berg D, Groneck P et al (2005) Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis. Pediatr Res 57:263–269

    Article  PubMed  Google Scholar 

  • D’Angio CT, Maniscalco WM (2002) The role of vascular growth factors in hyperoxia-induced injury to the developing lung. Front Biosci 7:d1609–d1623

    Article  PubMed  Google Scholar 

  • Dammann O, Leviton A (2014) Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res 75:376–380

    Article  PubMed  Google Scholar 

  • Danan C, Franco ML, Jarreau PH, Dassieu G, Chailley-Heu B, Bourbon J et al (2002) High concentrations of keratinocyte growth factor in airways of premature infants predicted absence of bronchopulmonary dysplasia. Am J Respir Crit Care Med 165:1384–1387

    Article  PubMed  Google Scholar 

  • Dommergues MA, Patkai J, Renauld JC, Evrard P, Gressens P (2000) Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium. Ann Neurol 47:54–63

    Article  CAS  PubMed  Google Scholar 

  • Dong Y, Speer CP (2015) Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed 100:F257–F263

    Article  PubMed  Google Scholar 

  • Eklind S, Mallard C, Arvidsson P, Hagberg H (2005) Lipopolysaccharide induces both a primary and a secondary phase of sensitization in the developing rat brain. Pediatr Res 58:112–116

    Article  CAS  PubMed  Google Scholar 

  • Ericson JE, Laughon MM (2015) Chorioamnionitis: implications for the neonate. Clin Perinatol 42:155–165, ix

    Article  PubMed  Google Scholar 

  • Fan X, Heijnen CJ, van der Kooij MA, Groenendaal F, van Bel F (2009) The role and regulation of hypoxia-inducible factor-1alpha expression in brain development and neonatal hypoxic-ischemic brain injury. Brain Res Rev 62:99–108

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Munoz Rodrigo F, Galan Henriquez G, Figueras Aloy J, Garcia-Alix Perez A (2014) Outcomes of very-low-birth-weight infants exposed to maternal clinical chorioamnionitis: a multicentre study. Neonatology 106:229–234

    Article  PubMed  Google Scholar 

  • Garcia-Ramallo E, Marques T, Prats N, Beleta J, Kunkel SL, Godessart N (2002) Resident cell chemokine expression serves as the major mechanism for leukocyte recruitment during local inflammation. J Immunol 169:6467–6473

    Article  CAS  PubMed  Google Scholar 

  • Genc MR, Onderdonk A (2011) Endogenous bacterial flora in pregnant women and the influence of maternal genetic variation. BJOG 118:154–163

    Article  CAS  PubMed  Google Scholar 

  • Gerber CE, Bruchelt G, Stegmann H, Schweinsberg F, Speer CP (1999) Presence of bleomycin-detectable free iron in the alveolar system of preterm infants. Biochem Biophys Res Commun 257:218–222

    Article  CAS  PubMed  Google Scholar 

  • Girard S, Kadhim H, Roy M, Lavoie K, Brochu ME, Larouche A et al (2009) Role of perinatal inflammation in cerebral palsy. Pediatr Neurol 40:168–174

    Article  PubMed  Google Scholar 

  • Girard S, Sebire H, Brochu ME, Briota S, Sarret P, Sebire G (2012) Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal inflammation and/or hypoxic-ischemic injuries. Brain Behav Immun 26:1331–1339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glaser K, Speer CP (2013) Toll-like receptor signaling in neonatal sepsis and inflammation: a matter of orchestration and conditioning. Expert Rev Clin Immunol 9:1239–1252

    Article  CAS  PubMed  Google Scholar 

  • Goldenberg RL, Andrews WW, Goepfert AR, Faye-Petersen O, Cliver SP, Carlo WA et al (2008) The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol 198(43):e41–e45

    Google Scholar 

  • Groneck P, Gotze-Speer B, Oppermann M, Eiffert H, Speer CP (1994) 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. Pediatrics 93:712–718

    CAS  PubMed  Google Scholar 

  • Guo H, Zhou H, Lu J, Qu Y, Yu D, Tong Y (2016) Vascular endothelial growth factor: an attractive target in the treatment of hypoxic/ischemic brain injury. Neural Regen Res 11:174–179

    Article  PubMed  PubMed Central  Google Scholar 

  • Hallman M, Curstedt T, Halliday HL, Saugstad OD, Speer CP (2013) Better neonatal outcomes: oxygen, surfactant and drug delivery. Preface. Neonatology 103:316–319

    Article  PubMed  Google Scholar 

  • Harju K, Glumoff V, Hallman M (2001) Ontogeny of toll-like receptors Tlr2 and Tlr4 in mice. Pediatr Res 49:81–83

    Article  CAS  PubMed  Google Scholar 

  • Harju K, Ojaniemi M, Rounioja S, Glumoff V, Paananen R, Vuolteenaho R et al (2005) Expression of toll-like receptor 4 and endotoxin responsiveness in mice during perinatal period. Pediatr Res 57:644–648

    Article  CAS  PubMed  Google Scholar 

  • Hartling L, Liang Y, Lacaze-Masmonteil T (2012) Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 97:F8–F17

    Article  PubMed  Google Scholar 

  • He Z, Zhu Y, Jiang H (2009) Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study. Respir Res 10:126

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hillman NH, Moss TJ, Nitsos I, Kramer BW, Bachurski CJ, Ikegami M et al (2008) Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr Res 63:388–393

    Article  CAS  PubMed  Google Scholar 

  • Hillman NH, Nitsos I, Berry C, Pillow JJ, Kallapur SG, Jobe AH (2011) Positive end-expiratory pressure and surfactant decrease lung injury during initiation of ventilation in fetal sheep. Am J Physiol Lung Cell Mol Physiol 301:L712–L720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hines EA, Sun X (2014) Tissue crosstalk in lung development. J Cell Biochem 115:1469–1477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hogmalm A, Bry M, Strandvik B, Bry K (2014) IL-1beta expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice. Am J Physiol Lung Cell Mol Physiol 306:L23–L34

    Article  CAS  PubMed  Google Scholar 

  • Huusko JM, Karjalainen MK, Mahlman M, Haataja R, Kari MA, Andersson S et al (2014) A study of genes encoding cytokines (IL6, IL10, TNF), cytokine receptors (IL6R, IL6ST), and glucocorticoid receptor (NR3C1) and susceptibility to bronchopulmonary dysplasia. BMC Med Genet 15:120

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Inatomi T, Oue S, Ogihara T, Hira S, Hasegawa M, Yamaoka S et al (2012) Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants. Pediatr Res 71:267–273

    Article  CAS  PubMed  Google Scholar 

  • Jaarsma AS, Braaksma MA, Geven WB, van Oeveren W, Bambang Oetomo S (2004) Activation of the inflammatory reaction within minutes after birth in ventilated preterm lambs with neonatal respiratory distress syndrome. Biol Neonate 86:1–5

    Article  CAS  PubMed  Google Scholar 

  • Jobe AH (2011) The new bronchopulmonary dysplasia. Curr Opin Pediatr 23:167–172

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones CA, Cayabyab RG, Kwong KY, Stotts C, Wong B, Hamdan H et al (1996) Undetectable interleukin (IL)-10 and persistent IL-8 expression early in hyaline membrane disease: a possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns. Pediatr Res 39:966–975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaindl AM, Favrais G, Gressens P (2009) Molecular mechanisms involved in injury to the preterm brain. J Child Neurol 24:1112–1118

    Article  PubMed  PubMed Central  Google Scholar 

  • Kallapur SG, Jobe AH, Ikegami M, Bachurski CJ (2003) Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung. Am J Respir Crit Care Med 167:779–786

    Article  PubMed  Google Scholar 

  • Kemp MW (2014) Preterm birth, intrauterine infection, and fetal inflammation. Front Immunol 5:574

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Khwaja O, Volpe JJ (2008) Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 93:F153–F161

    Article  CAS  PubMed  Google Scholar 

  • Kim KS (2003) Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 4:376–385

    Article  CAS  PubMed  Google Scholar 

  • Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM (2015) Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol 213:S29–S52

    Article  PubMed  PubMed Central  Google Scholar 

  • Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J (2001) Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest 107:1529–1536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kollmann TR, Crabtree J, Rein-Weston A, Blimkie D, Thommai F, Wang XY et al (2009) Neonatal innate TLR-mediated responses are distinct from those of adults. J Immunol 183:7150–7160

    Article  CAS  PubMed  Google Scholar 

  • Kollmann TR, Levy O, Montgomery RR, Goriely S (2012) Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37:771–783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korzeniewski SJ, Romero R, Cortez J, Pappas A, Schwartz AG, Kim CJ et al (2014) A “multi-hit” model of neonatal white matter injury: cumulative contributions of chronic placental inflammation, acute fetal inflammation and postnatal inflammatory events. J Perinat Med 42:731–743

    Article  PubMed  PubMed Central  Google Scholar 

  • Kramer BW, Moss TJ, Willet KE, Newnham JP, Sly PD, Kallapur SG et al (2001) Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med 164:982–988

    Article  CAS  PubMed  Google Scholar 

  • Kramer BW, Kramer S, Ikegami M, Jobe AH (2002) Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 283:L452–L459

    Article  CAS  PubMed  Google Scholar 

  • Kramer BW, Ladenburger A, Kunzmann S, Speer CP, Been JV, van Iwaarden JF et al (2009) Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep. Am J Obstet Gynecol 200:195 e191–110

    Article  CAS  Google Scholar 

  • Kroon AA, Wang J, Huang Z, Cao L, Kuliszewski M, Post M (2010) Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume. Pediatr Res 68:63–69

    Article  CAS  PubMed  Google Scholar 

  • Kuang PP, Zhang XH, Rich CB, Foster JA, Subramanian M, Goldstein RH (2007) Activation of elastin transcription by transforming growth factor-beta in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 292:L944–L952

    Article  CAS  PubMed  Google Scholar 

  • Kunig AM, Balasubramaniam V, Markham NE, Seedorf G, Gien J, Abman SH (2006) Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia. Am J Physiol Lung Cell Mol Physiol 291:L1068–L1078

    Article  CAS  PubMed  Google Scholar 

  • Kunzmann S, Seher A, Kramer BW, Schenk R, Schutze N, Jakob F et al (2008) Connective tissue growth factor does not affect transforming growth factor-beta 1-induced Smad3 phosphorylation and T lymphocyte proliferation inhibition. Int Arch Allergy Immunol 147:152–160

    Article  CAS  PubMed  Google Scholar 

  • Lal CV, Ambalavanan N (2015) Genetic predisposition to bronchopulmonary dysplasia. Semin Perinatol 39:584–591

    Article  PubMed  Google Scholar 

  • Lassus P, Heikkila P, Andersson LC, von Boguslawski K, Andersson S (2003) Lower concentration of pulmonary hepatocyte growth factor is associated with more severe lung disease in preterm infants. J Pediatr 143:199–202

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Kim HJ, Choi SJ, Oh SY, Kim JS, Roh CR et al (2015) Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?: effect of gestational age at delivery. J Perinat Med 43:259–267

    PubMed  Google Scholar 

  • Leviton A, Allred EN, Kuban KC, Hecht JL, Onderdonk AB, O’Shea TM et al (2010) Microbiologic and histologic characteristics of the extremely preterm infant’s placenta predict white matter damage and later cerebral palsy. The ELGAN study. Pediatr Res 67:95–101

    Article  PubMed  PubMed Central  Google Scholar 

  • Levy BD, Serhan CN (2014) Resolution of acute inflammation in the lung. Annu Rev Physiol 76:467–492

    Article  CAS  PubMed  Google Scholar 

  • Levy O, Wynn JL (2014) A prime time for trained immunity: innate immune memory in newborns and infants. Neonatology 105:136–141

    Article  CAS  PubMed  Google Scholar 

  • Li WJ, Mao FX, Chen HJ, Qian LH, Buzby JS (2015) Treatment with UDP-glucose, GDNF, and memantine promotes SVZ and white matter self-repair by endogenous glial progenitor cells in neonatal rats with ischemic PVL. Neuroscience 284:444–458

    Article  CAS  PubMed  Google Scholar 

  • Lozano SM, Newnam KM (2016) Modalities of mechanical ventilation: volume-targeted versus pressure-limited. Adv Neonatal Care 16:99–107

    Article  PubMed  Google Scholar 

  • Lukkarinen H, Hogmalm A, Lappalainen U, Bry K (2009) Matrix metalloproteinase-9 deficiency worsens lung injury in a model of bronchopulmonary dysplasia. Am J Respir Cell Mol Biol 41:59–68

    Article  CAS  PubMed  Google Scholar 

  • Martin RJ, Fanaroff AA (2013) The preterm lung and airway: past, present, and future. Pediatr Neonatol 54:228–234

    Article  PubMed  Google Scholar 

  • May M, Marx A, Seidenspinner S, Speer CP (2004) Apoptosis and proliferation in lungs of human fetuses exposed to chorioamnionitis. Histopathology 45:283–290

    Article  CAS  PubMed  Google Scholar 

  • Mesples B, Plaisant F, Gressens P (2003) Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice. Brain Res Dev Brain Res 141:25–32

    Article  CAS  PubMed  Google Scholar 

  • Miller JD, Benjamin JT, Kelly DR, Frank DB, Prince LS (2010) Chorioamnionitis stimulates angiogenesis in saccular stage fetal lungs via CC chemokines. Am J Physiol Lung Cell Mol Physiol 298:L637–L645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morley CJ (2010) CPAP and low oxygen saturation for very preterm babies? N Engl J Med 362:2024–2026

    Article  CAS  PubMed  Google Scholar 

  • Murch SH, Costeloe K, Klein NJ, MacDonald TT (1996a) Early production of macrophage inflammatory protein-1 alpha occurs in respiratory distress syndrome and is associated with poor outcome. Pediatr Res 40:490–497

    Article  CAS  PubMed  Google Scholar 

  • Murch SH, Costeloe K, Klein NJ, Rees H, McIntosh N, Keeling JW et al (1996b) Mucosal tumor necrosis factor-alpha production and extensive disruption of sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory distress syndrome. Pediatr Res 40:484–489

    Article  CAS  PubMed  Google Scholar 

  • Nanthakumar N, Meng D, Goldstein AM, Zhu W, Lu L, Uauy R et al (2011) The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS One 6:e17776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narimanbekov IO, Rozycki HJ (1995) Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model. Exp Lung Res 21:239–254

    Article  CAS  PubMed  Google Scholar 

  • Nguyen CN, Schnulle PM, Chegini N, Luo X, Koenig JM (2010) Neonatal neutrophils with prolonged survival secrete mediators associated with chronic inflammation. Neonatology 98:341–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen HA, Rajaram MV, Meyer DA, Schlesinger LS (2012) Pulmonary surfactant protein A and surfactant lipids upregulate IRAK-M, a negative regulator of TLR-mediated inflammation in human macrophages. Am J Physiol Lung Cell Mol Physiol 303:L608–L616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Normann E, Lacaze-Masmonteil T, Eaton F, Schwendimann L, Gressens P, Thebaud B (2009) A novel mouse model of Ureaplasma-induced perinatal inflammation: effects on lung and brain injury. Pediatr Res 65:430–436

    Article  PubMed  Google Scholar 

  • O’Carroll SJ, Kho DT, Wiltshire R, Nelson V, Rotimi O, Johnson R et al (2015) Pro-inflammatory TNFalpha and IL-1beta differentially regulate the inflammatory phenotype of brain microvascular endothelial cells. J Neuroinflammation 12:131

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • O’Hare FM, William Watson R, Molloy EJ (2013) Toll-like receptors in neonatal sepsis. Acta Paediatr 102:572–578

    Article  PubMed  CAS  Google Scholar 

  • Paananen R, Husa AK, Vuolteenaho R, Herva R, Kaukola T, Hallman M (2009) Blood cytokines during the perinatal period in very preterm infants: relationship of inflammatory response and bronchopulmonary dysplasia. J Pediatr 154:39–43 e33

    Article  CAS  PubMed  Google Scholar 

  • Pang Y, Rodts-Palenik S, Cai Z, Bennett WA, Rhodes PG (2005) Suppression of glial activation is involved in the protection of IL-10 on maternal E. coli induced neonatal white matter injury. Brain Res Dev Brain Res 157:141–149

    Article  CAS  PubMed  Google Scholar 

  • Prince LS, Dieperink HI, Okoh VO, Fierro-Perez GA, Lallone RL (2005) Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung. Dev Dyn 233:553–561

    Article  CAS  PubMed  Google Scholar 

  • Reyburn B, Martin RJ, Prakash YS, MacFarlane PM (2012) Mechanisms of injury to the preterm lung and airway: implications for long-term pulmonary outcome. Neonatology 101:345–352

    Article  PubMed  Google Scholar 

  • Ricard JD, Dreyfuss D, Saumon G (2001) Production of inflammatory cytokines in ventilator-induced lung injury: a reappraisal. Am J Respir Crit Care Med 163:1176–1180

    Article  CAS  PubMed  Google Scholar 

  • Sarelius IH, Glading AJ (2015) Control of vascular permeability by adhesion molecules. Tissue Barriers 3:e985954

    Article  PubMed  CAS  Google Scholar 

  • Saugstad OD (2005) Oxidative stress in the newborn – a 30-year perspective. Biol Neonate 88:228–236

    Article  CAS  PubMed  Google Scholar 

  • Schmitz T, Ritter J, Mueller S, Felderhoff-Mueser U, Chew LJ, Gallo V (2011) Cellular changes underlying hyperoxia-induced delay of white matter development. J Neurosci 31:4327–4344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith RE (1996) Chemotactic cytokines mediate leukocyte recruitment in fibrotic lung disease. Biol Signals 5:223–231

    Article  CAS  PubMed  Google Scholar 

  • Speer CP (2006a) Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med 11:354–362

    Article  PubMed  Google Scholar 

  • Speer CP (2006b) Pulmonary inflammation and bronchopulmonary dysplasia. J Perinatol 26(Suppl 1):S57–S62; discussion S63–54

    Article  CAS  PubMed  Google Scholar 

  • Speer CP (2009) Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia. Neonatology 95:353–361

    Article  CAS  PubMed  Google Scholar 

  • Speer CP (2011) Neonatal respiratory distress syndrome: an inflammatory disease? Neonatology 99:316–319

    Article  CAS  PubMed  Google Scholar 

  • Speer CP, Pabst MJ, Hedegaard HB, Rest RF, Johnston RB Jr (1984) Enhanced release of oxygen metabolites by monocyte-derived macrophages exposed to proteolytic enzymes: activity of neutrophil elastase and cathepsin G. J Immunol 133:2151–2156

    CAS  PubMed  Google Scholar 

  • Speer CP, Gahr M, Wieland M, Eber S (1988) Phagocytosis-associated functions in neonatal monocyte-derived macrophages. Pediatr Res 24:213–216

    Article  CAS  PubMed  Google Scholar 

  • Speer CP, Ruess D, Harms K, Herting E, Gefeller O (1993) Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome. Pediatrics 91:794–799

    CAS  PubMed  Google Scholar 

  • Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP et al (2011) Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 127:817–826

    Article  PubMed  PubMed Central  Google Scholar 

  • Stridh L, Smith PL, Naylor AS, Wang X, Mallard C (2011) Regulation of toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia. J Neuroinflammation 8:45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stridh L, Ek CJ, Wang X, Nilsson H, Mallard C (2013) Regulation of toll-like receptors in the choroid plexus in the immature brain after systemic inflammatory stimuli. Transl Stroke Res 4:220–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strunk T, Doherty D, Jacques A, Simmer K, Richmond P, Kohan R et al (2012) Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants. Pediatrics 129:e134–e141

    Article  PubMed  Google Scholar 

  • Strunk T, Inder T, Wang X, Burgner D, Mallard C, Levy O (2014) Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis 14:751–762

    Article  PubMed  PubMed Central  Google Scholar 

  • Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140:805–820

    Article  CAS  PubMed  Google Scholar 

  • Thebaud B, Abman SH (2007) Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med 175:978–985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thebaud B, Ladha F, Michelakis ED, Sawicka M, Thurston G, Eaton F et al (2005) Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation 112:2477–2486

    Article  CAS  PubMed  Google Scholar 

  • Thomas W, Speer CP (2011) Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology 99:177–187

    Article  PubMed  Google Scholar 

  • Thomas W, Speer CP (2014) Chorioamnionitis is essential in the evolution of bronchopulmonary dysplasia – the case in favour. Paediatr Respir Rev 15:49–52

    PubMed  Google Scholar 

  • Thomas W, Seidenspinner S, Kawczynska-Leda N, Kramer BW, Chmielnicka-Kopaczyk M, Marx A et al (2008) Systemic fetal inflammation and reduced concentrations of macrophage migration inhibitory factor in tracheobronchial aspirate fluid of extremely premature infants. Am J Obstet Gynecol 198(64):e61–e66

    Google Scholar 

  • Turunen R, Nupponen I, Siitonen S, Repo H, Andersson S (2006) Onset of mechanical ventilation is associated with rapid activation of circulating phagocytes in preterm infants. Pediatrics 117:448–454

    Article  PubMed  Google Scholar 

  • Ueda K, Cho K, Matsuda T, Okajima S, Uchida M, Kobayashi Y et al (2006) A rat model for arrest of alveolarization induced by antenatal endotoxin administration. Pediatr Res 59:396–400

    Article  CAS  PubMed  Google Scholar 

  • Varughese R, Nayak JL, LoMonaco M, O’Reilly MA, Ryan RM, D’Angio CT (2003) Effects of hyperoxia on tumor necrosis factor alpha and Grobeta expression in newborn rabbit lungs. Lung 181:335–346

    Article  CAS  PubMed  Google Scholar 

  • Viscardi RM (2012) Perinatal inflammation and lung injury. Semin Fetal Neonatal Med 17:30–35

    Article  PubMed  Google Scholar 

  • Viscardi RM (2014) Ureaplasma species: role in neonatal morbidities and outcomes. Arch Dis Child Fetal Neonatal Ed 99:F87–F92

    Article  PubMed  Google Scholar 

  • Viscardi RM, Muhumuza CK, Rodriguez A, Fairchild KD, Sun CC, Gross GW et al (2004) Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res 55:1009–1017

    Article  CAS  PubMed  Google Scholar 

  • Volpe JJ (2008) Postnatal sepsis, necrotizing entercolitis, and the critical role of systemic inflammation in white matter injury in premature infants. J Pediatr 153:160–163

    Article  PubMed  PubMed Central  Google Scholar 

  • Vuichard D, Ganter MT, Schimmer RC, Suter D, Booy C, Reyes L et al (2005) Hypoxia aggravates lipopolysaccharide-induced lung injury. Clin Exp Immunol 141:248–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagenaar GT, ter Horst SA, van Gastelen MA, Leijser LM, Mauad T, van der Velden PA et al (2004) Gene expression profile and histopathology of experimental bronchopulmonary dysplasia induced by prolonged oxidative stress. Free Radic Biol Med 36:782–801

    Article  CAS  PubMed  Google Scholar 

  • Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274:19403–19410

    Article  CAS  PubMed  Google Scholar 

  • Wilson MR, Choudhury S, Takata M (2005) Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice. Am J Physiol Lung Cell Mol Physiol 288:L599–L607

    Article  CAS  PubMed  Google Scholar 

  • Wu YW (2002) Systematic review of chorioamnionitis and cerebral palsy. Ment Retard Dev Disabil Res Rev 8:25–29

    Article  PubMed  Google Scholar 

  • Yamamoto M, Takeda K (2010) Current views of toll-like receptor signaling pathways. Gastroenterol Res Pract 2010:240365

    Article  PubMed  PubMed Central  Google Scholar 

  • Yi M, Jankov RP, Belcastro R, Humes D, Copland I, Shek S et al (2004) Opposing effects of 60% oxygen and neutrophil influx on alveologenesis in the neonatal rat. Am J Respir Crit Care Med 170:1188–1196

    Article  PubMed  Google Scholar 

  • Yoon BH, Romero R, Jun JK, Park KH, Park JD, Ghezzi F et al (1997) Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 177:825–830

    Article  CAS  PubMed  Google Scholar 

  • Yu KH, Li J, Snyder M, Shaw GM, O’Brodovich HM (2016) The genetic predisposition to bronchopulmonary dysplasia. Curr Opin Pediatr 28:318–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Zhou J, Xu B, Chen C, Shi W (2015) Different expressions of TLRs and related factors in peripheral blood of preterm infants. Int J Clin Exp Med 8:4108–4114

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Gilmore BJ, Young SL (1997) Expression of transforming growth factor-beta receptors during hyperoxia-induced lung injury and repair. Am J Physiol 273:L355–L362

    CAS  PubMed  Google Scholar 

  • Zlotnik A, Yoshie O (2012) The chemokine superfamily revisited. Immunity 36:705–716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Children’s Hospital, University of Würzburg, Würzburg, Germany

    Kirsten Glaser & Christian P. Speer

Authors
  1. Kirsten Glaser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian P. Speer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kirsten Glaser or Christian P. Speer .

Editor information

Editors and Affiliations

  1. Department of Pediatrics Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy

    Giuseppe Buonocore

  2. Department of Pediatrics Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy

    Rodolfo Bracci

  3. Liverpool Women’s Hospital Neonatal Unit, Liverpool, UK

    Michael Weindling

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Glaser, K., Speer, C.P. (2018). Prenatal and Postnatal Inflammatory Mechanisms. In: Buonocore, G., Bracci, R., Weindling, M. (eds) Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29489-6_154

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-29489-6_154

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29487-2

  • Online ISBN: 978-3-319-29489-6

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation