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Commentary

Neonatology 2012;102:59–60 DOI: 10.1159/000336865

Is Lung Surfactant Ready ‘to Protect and to Serve’ in Necrotizing Enterocolitis? Commentary on F.E. Canpolat et al.: Effects of Enterally Administered Surfactant in a Rat

Model of Necrotizing Enterocolitis (Neonatology 2012;102:53–58)

Frans J. Walther

Division of Neonatology, Department of Pediatrics, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden , The Netherlands

the SOD and GPx content of the porcine surfactant (Curosurf) used [3] , whereas the lower MDA levels, which reflect reduced lipid peroxidation, may be due to an over-load of surfactant lipids in the gut. All in all, enteral sur-factant administration increased antioxidant enzyme ac-tivity and decreased lipid peroxidation, and tipped the balance between the production of reactive oxygen spe-cies and the gut’s ability to detoxify them in favor of re-duced oxidative stress. However, this did not result in less histological damage to the gut and suggests that oxidative stress in the pathogenesis of NEC is not due to a deficient antioxidant capacity, but the result of an excess produc-tion of reactive oxygen species.

What if the authors would have used lung surfactant for its antioxidant properties? In that case, the same result could have been obtained by administering a less-expen-sive liposomal preparation of SOD, catalase, and/or GPx. Davis et al. [4] showed for example that intratracheal ad-ministration of recombinant human CuZn SOD (rhSOD) to preterm infants increases the concentration and activ-ity of SOD in tracheal aspirates and serum and may re-duce early pulmonary injury. Likewise, early intratrache-al rhSOD treatment improves oxygenation in premature lambs with RDS and prevents the development of pulmo-nary hypertension [5] . What if the authors decided to give

Necrotizing enterocolitis (NEC) is a common gastro-intestinal emergency in the neonatal intensive care unit and associated with a high mortality. The precise patho-genesis of NEC is incompletely understood, but is clearly multifactorial [1] . Prematurity is the most important risk factor that, in combination with formula feeding, intesti-nal hypoxic-ischemic injury, and colonization of the gut with pathogenic bacteria, may lead to activation of the inflammatory cascade that precipitates NEC. Antenatal glucocorticoids, early feeding with human breast milk, careful feeding advancement, and prophylactic probiotic administration reduce the risk of NEC in preterm in-fants, but primary prevention continues to be a holy grail in neonatology.

In this issue of Neonatology , Canpolat et al. [2] exam-ine whether 5 days of enteral administration of high dos-es of lung surfactant (400 mg/kg of Curosurf � per day) protect against the development of NEC in newborn rats exposed to 5 min of hypoxia, followed by 5 min of hyper-oxia. Enteral treatment with lung surfactant did not pro-tect against the histological changes of NEC, but in-creased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity and reduced malondialdehyde (MDA) levels. The increase in antioxidant enzyme activ-ity in the gut of surfactant-treated rats probably reflects

Received: January 25, 2012 Accepted: January 28, 2012 Published online: April 11, 2012

Frans J. Walther Division of Neonatology, Department of PediatricsWillem-Alexander Children’s Hospital, Leiden University Medical Center, J6-SAlbinusdreef 2, NL–2333 ZA Leiden (The Netherlands) Tel. +31 71 526 2957, E-Mail fwalther   @   lumc.nl

© 2012 S. Karger AG, Basel1661–7800/12/1021–0059$38.00/0

Accessible online at:www.karger.com/neo

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Walther

Neonatology 2012;102:59–60 60

lung surfactant for its high lipid concentration? In that case, the high phospholipid content of Curosurf (80 mg/ml) could contribute to gut protection through a barrier action or anti-bacterial activity. And what if the authors decided to give lung surfactant for its surfactant proteins (SP)? Clinical surfactants contain a total of 2(–3)% of SP-B and SP-C which are essential for optimal surface ac-tivity of surfactant and normal lung function, but lack SP-A and SP-D which play an important role in innate immunity of the lung and might have slowed the inflam-matory cascade in the gut. So, in retrospect, use of a na-tive instead of a clinical surfactant might have worked better through the presence of SP-A and SP-D.

The paper by Canpolat et al. [2] does not resolve how to prevent and treat NEC, but is a fine example of think-ing outside the box: enteral administration of lung sur-

factant increases the gut’s defense against reactive oxida-tive species, but does not slow down the destruction of the bowels during NEC. The central question in NEC is of course how to slow or, preferably, interrupt the inflam-matory cascade. Recent insights about the facilitating function of Toll-like receptor 4 (TLR4) may offer a new window of opportunity here [6] . Without any doubt, pre-vention of NEC will have a greater impact on mortality and morbidity than treatment when the gut is already on fire. Until the magic bullet comes along, current thinking about prevention focuses on feeding the infant with the mother’s expressed breast milk, use of enteral antibiotics, and administration of probiotic and/or prebiotic agents, growth factors, anticytokine agents, and glucocorticoids [1] . More research in this field is badly needed as clinical surfactant is not ready to protect and serve in NEC.

References

1 Neu J, Walker WA: Necrotizing enterocoli-tis. N Engl J Med 2011; 364: 255–264.

2 Canpolat FE, Yurdakök M, Ersin SC: Effects of enterally administered surfactant in a rat model of necrotizing enterocolitis. Neona-tology 2012;102:53–58.

3 Dani C, Buonocore G, Longini M, Felici C, Rodriguez A, Corsini I, Rubaltelli FF: Super-oxide dismutase and catalase activity in nat-urally derived commercial surfactants. Pedi-atr Pulmonol 2009; 44: 1125–1131.

4 Davis JM, Rosenfeld WN, Richter SE, Parad MR, Gewolb IH, Spitzer AR, Carlo WA, Couser RJ, Price A, Flaster E, Kassem N, Ed-wards L, Tierney J, Horowitz S: Safety and pharmacokinetics of multiple doses of re-combinant human CuZn superoxide dis-mutase administered intratracheally to pre-mature neonates with respiratory distress syndrome. Pediatrics 1997; 100: 24–30.

5 Kinsella JP, Parker TA, Davis JM, Abman SH: Superoxide dismutase improves gas ex-change and pulmonary hemodynamics in premature lambs. Am J Respir Crit Care Med 2005; 172: 745–749.

6 Nanthakumar N, Meng D, Goldstein AM, Zhu W, Lu L, Uauy R, Llanos A, Claud EC, Walker WA: The mechanism of excessive in-testinal inflammation in necrotizing entero-colitis: an immature innate immune re-sponse. PLoS One 2011; 6:e17776.

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