The pathogenesis of neonatal group B Streptococcus (GBS) lung infection may be associated with surfactant dysfunction or deficiency. This study aimed to investigate the efficacy of surfactants on early postnatal GBS infection in ventilated newborn rabbit lungs.
A near-term newborn rabbit model was established by intratracheal GBS instillation immediately at birth, followed by mechanical ventilation. At postnatal 1 h, a porcine surfactant was given intratracheally at 100 or 200 mg/kg. After 6 h, animals were euthanized, and lung and blood samples were collected for bacterial counting. Lung histopathology and messenger RNA (mRNA) expression of inflammatory mediators, surfactant proteins, and growth factors in lung tissue were assessed.
The surfactants significantly suppressed (by >50%) pulmonary bacterial proliferation and systemic translocation, alleviated lung inflammatory injury, and improved alveolar expansion by morphometry, in favor of high-dose surfactants. Though the survival rate and lung mechanics were not improved, the surfactants significantly suppressed mRNA expression of proinflammatory mediators, while that for surfactant proteins and growth factors was differentially expressed, compared to the control and GBS infection groups.
Exogenous surfactants may provide a therapeutic alternative for neonatal lung infection by suppressing pulmonary GBS proliferation and translocation into systemic circulation, alleviating inflammatory injury and regulating growth factor expression.
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Verani, J. R., McGee, L. & Schrag, S. J. Division of bacterial diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease-revised guidelines from CDC, 2010. MMWR Recomm. Rep. 59, 1–36 (2010).
Doran, K. S. & Nizet, V. Molecular pathogenesis of neonatal group B streptococcal infection: no longer in its infancy. Mol. Microbiol. 54, 23–31 (2004).
Stoll, B. J. et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 127, 817–826 (2011).
Dong, Y. et al. Group B Streptococcus causes severe sepsis in term neonates: 8 years experience of a major Chinese neonatal unit. World J. Pediatr. 13, 314–320 (2017).
Edmond, K. M. et al. Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 379, 547–556 (2012).
Madrid, L. et al. Infant group B streptococcal disease incidence and serotypes worldwide: systematic review and meta-analyses. Clin. Infect. Dis. 65, 160–172 (2017).
Yeo, K. T. et al. Long-term outcomes after group B streptococcus infection: a cohort study. Arch. Dis. Child 104, 172–178 (2019).
Seger, N. & Soll, R. Animal derived surfactant extract for treatment of respiratory distress syndrome. Cochrane Database Syst. Rev. 2, CD007836 (2009).
Qian, L. et al. Effects of positive end-expiratory pressure, inhaled nitric oxide and surfactant on expression of proinflammatory cytokines and growth factors in preterm piglet lungs. Pediatr. Res. 64, 17–23 (2008).
Fetter, W. P. et al. Surfactant replacement therapy in neonates with respiratory failure due to bacterial sepsis. Acta Paediatr. 84, 14–16 (1995).
Herting, E. et al. Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Pediatrics 106, 957–964 (2000).
Tan, K., Lai, N. M. & Sharma, A. Surfactant for bacterial pneumonia in late preterm and term infants. Cochrane Database Syst. Rev. 2, CD008155 (2012).
Taylor G. et al. Surfactant administration in preterm infants: drug development opportunities. J. Pediatr. 208, 163–168 (2019).
Rauprich, P. et al. Influence of modified natural or synthetic surfactant preparations on growth of bacteria causing infections in the neonatal period. Clin. Diagn. Lab. Immunol. 7, 817–822 (2000).
Bouhafs, R. K. et al. Direct and phagocyte-mediated lipid peroxidation of lung surfactant by group B streptococci. Lung 178, 317–329 (2000).
Doran, K. S. et al. Group B streptococcal beta-hemolysin/cytolysin promotes invasion of human lung epithelial cells and the release of interleukin-8. J. Infect. Dis. 185, 196–203 (2002).
Hensler, M. E. et al. Virulence role of group B Streptococcus beta-hemolysin/cytolysin in a neonatal rabbit model of early-onset pulmonary infection. J. Infect. Dis. 191, 1287–1291 (2005).
Herting, E. et al. Experimental neonatal group B streptococcal pneumonia: effect of a modified porcine surfactant on bacterial proliferation in ventilated near-term rabbits. Pediatr. Res. 36, 784–791 (1994).
Herting, E. et al. Surfactant improves lung function and mitigates bacterial growth in immature ventilated rabbits with experimentally induced neonatal group B streptococcal pneumonia. Arch. Dis. Child Fetal Neonatal Ed. 76, 3–8 (1997).
Wright, J. R. Immunoregulatory functions of surfactant proteins. Nat. Rev. Immunol. 5, 58–68 (2005).
Wang, H. et al. Surfactant reduced the mortality of neonates with birth weight >1500g and hypoxemic respiratory failure: a survey from an emerging NICU network. J. Perinatol. 37, 645–651 (2017).
Zhang, L. et al. Mortality of neonatal respiratory failure from Chinese Northwest NICU network. J. Matern. Fetal Neonatal Med. 30, 2105–2111 (2017).
Sun, B. et al. Application of a new ventilator-multi-plethysmograph system for testing efficacy of surfactant replacement in newborn rabbits. Eur. Respir. J. 4, 364–370 (1991).
Zhu, G. F. et al. Combined surfactant therapy and inhaled nitric oxide in rabbits with oleic acid-induced acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 158, 437–443 (1998).
Payne, N. R. et al. Correlation of clinical and pathologic findings in early onset neonatal group B streptococcal infection with disease severity and prediction of outcome. Pediatr. Infect. Dis. J. 7, 836–847 (1988).
Rider, E. D. et al. Different ventilation strategies alter surfactant responses in preterm rabbits. J. Appl. Physiol. 73, 2089–2096 (1992).
Siew, M. L. et al. Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits. Pediatr. Res. 70, 50–55 (2011).
Nizet, V. et al. Group B streptococcal beta-hemolysin expression is associated with injury of lung epithelial cells. Infect. Immun. 64, 3818–3826 (1996).
Zhu, Y. et al. Different effects of surfactant and inhaled nitric oxide in modulation of inflammatory injury in ventilated piglet lungs. Pulm. Pharm. Ther. 18, 303–313 (2005).
Zhao, D. H. et al. Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide. Intens. Care Med. 26, 229–238 (2000).
Hu, X. et al. Mitigation of meconium-induced lung injury by surfactant and inhaled nitric oxide is associated with suppression of nuclear transcription factor kappa B. Biol. Neonate 87, 73–81 (2005).
Puliti, M. et al. Toll-like receptor 2 deficiency is associated with enhanced severity of group B streptococcal disease. Infect. Immun. 77, 1524–1531 (2009).
Glaser, K. & Speer, C. P. Toll-like receptor signaling in neonatal sepsis and inflammation: a matter of orchestration and conditioning. Expert Rev. Clin. Immunol. 9, 1239–1252 (2013).
Goodrum, K. J. & Poulson-Dunlap, J. Cytokine responses to group B streptococci induce nitric oxide production in respiratory epithelial cells. Infect. Immun. 70, 49–54 (2002).
Hu, X., Guo, C. & Sun, B. Inhaled nitric oxide attenuates hyperoxic and inflammatory injury without alteration of phosphatidylcholine synthesis in rat lungs. Pulmon. Pharm. Ther. 20, 75–84 (2007).
Gong, X. et al. Inhaled nitric oxide alleviates hyperoxia suppressed phosphatidylcholine synthesis in endotoxin-induced injury in mature rat lungs. Respir. Res. 7, 5 (2006).
Sun, Z. et al. Anti-inflammatory effects of inhaled nitric oxide are optimized at lower oxygen concentration in experimental Klebsiella pneumoniae pneumonia. Inflam. Res. 55, 430–440 (2006).
Deng, J. C. & Standiford, T. J. Growth factors and cytokines in acute lung injury. Compr. Physiol. 1, 81–104 (2011).
Narasaraju, T. A. et al. Expression profile of IGF system during lung injury and recovery in rats exposed to hyperoxia: a possible role of IGF-1 in alveolar epithelial cell proliferation and differentiation. J. Cell. Biochem. 97, 984–998 (2006).
He, L. et al. Protective role of glucocorticosteroid prior to endotoxin exposure in cultured neonatal type II alveolar epithelial cells. Pulm. Pharm. Ther. 52, 18–26 (2018).
We thank Dr. Yi Liu for measurement with transmission electron microscopy, Dr. Dongmei Ding and Prof. Lian Chen for measurement of lung histology and morphometry. This study was supported by a grant from the National Natural Science Foundation (No. 81501288 to Y.D.).