title: Meconium is a source of pro-inflammatory substances and can induce cytokine production in cultured A549 epithelial cells.
abstract: Inflammation plays an important role in the pathogenesis of meconium aspiration syndrome, and pneumonitis is one of the major characteristics. We have previously shown that meconium has chemotactic properties because of the presence of IL-8. We hypothesize that IL-8 and other proinflammatory substances in meconium may amplify inflammation in meconium aspiration syndrome, inducing endogenous cytokine production by lung epithelial cells. We measured proinflammatory substances in first-pass meconium from healthy newborns and evaluated the effect of sterile meconium on cytokine production in cultured A549 alveolar epithelial cells in vitro. IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha were measured by ELISA, and heme was measured spectrophotometrically. After incubation of meconium samples with A549 cells, cytokine concentrations in the supernatant were measured. Meconium samples contained variable amounts of IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and heme. On stimulation of A549 cells with meconium, the IL-8 concentration in the culture supernatant significantly increased above baseline measurements, whereas tumor necrosis factor-alpha showed a variable pattern and IL-1beta or IL-6 remained unchanged. There was no quantitative relationship between the concentration of the measured cytokines and heme in meconium and cytokine release by the A549 cells after meconium exposure. Meconium contains proinflammatory substances. All samples induced IL-8 release and some induced tumor necrosis factor-alpha release in cultured A549 epithelial cells. We speculate that proinflammatory substances in meconium can induce lung inflammation in meconium aspiration syndrome in two ways: directly via cytokines and heme present in meconium and indirectly by inducing cytokine release by the epithelial lung cells.
authors.affiliation: Neonatal Unit, Department of Pediatrics, Juliana Children's Hospital, 2506 LP The Hague, The Netherlands. a.debeaufort@jkz-rkz.nl
authors.forename: Arnout Jan
authors.initials: AJ
authors.lastname: de Beaufort
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Bakker
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Schrama
authors.forename: Howard M
authors.initials: HM
authors.lastname: Berger
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006418:Heme / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008470:Meconium / Q000276:immunology*; D011247:Pregnancy; D020545:Respiratory Mucosa / Q000166:cytology
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D006418:Heme