Abstract
We are interested in determining whether premature birth alters expression of counterregulatory cytokines which modulate lung inflammation. Production of proinflammatory cytokines tumor necrosis factor α, IL-1β, and IL-8 is regulated in part by the antiinflammatory cytokine IL-10. For preterm newborns with hyaline membrane disease, deficiencies in the ability of lung macrophages to express antiinflammatory cytokines may predispose to chronic lung inflammation. We compared the expression of pro- and antiinflammatory cytokines at the mRNA and protein level in the lungs of preterm and term newborns with acute respiratory failure from hyaline membrane disease or meconium aspiration syndrome. Four sequential bronchoalveolar lavage (BAL) samples were obtained during the first 96 h of life from all patients. All patients rapidly developed an influx of neutrophils and macrophages. Over time, cell populations in both groups became relatively enriched with macrophages. The expression of proinflammatory cytokine mRNA and/or protein was present in all samples from both patient groups. In contrast, IL-10 mRNA was undetectable in most of the cell samples from preterm infants and present in the majority of cell samples from term infants. IL-10 concentrations were undetectable in lavage fluid from preterm infants with higher levels in a few of the BAL samples from term infants. These studies demonstrate that1) IL-10 mRNA and protein expression by lung inflammatory cells is related to gestational age and 2) during the first 96 h of life neutrophil cell counts and IL-8 expression decrease in BAL from term infants, but remain unchanged in BAL samples from preterm infants.
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Abbreviations
- HMD:
-
hyaline membrane disease
- MAS:
-
meconium aspiration syndrome
- ARF:
-
acute respiratory failure
- ARDS:
-
adult respiratory distress syndrome
- CLD:
-
chronic lung disease
- BAL:
-
bronchoalveolar lavage
- TNF:
-
tumor necrosis factor
- RT:
-
reverse transcriptase
- PCR:
-
polymerase chain reaction
- IFN:
-
interferon
References
Coalson JJ, Kuchl TJ, Prihoda TJ, deLemos RA 1988 Diffuse alveolar damage in the evolution of bronchopulmonary dysplasia in the baboon. Pediatr Res 24: 357–366.
deLemos RA, Yoder B, McCurnin D, Kinsella J, Clark R, Null D 1992 The use of high-frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation (ECMO) in the management of the term/near term infant with respiratory failure. Early Hum Dev 29: 299–303.
Minoo P, Segura L, deLemos R, Coalson JJ, King RJ 1991 Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia. Am J Physiol 261:L386–L392.
Ogden BE, Murphy S, Saunders GC, Johnson JD 1983 Lung lavage of newborns with respiratory distress syndrome: prolonged neutrophil influx is associated with bronchopulmonary dysplasia. Chest 83: 31–33.
Bonikos DS, Bensch KG, Merit TA 1988 In: Northway WH, Boynton BR (eds) Bronchopulmonary Dysplasia. Blackwell, Boston, 33–58.
Edwards DK, Colby TV, Northway WH 1979 Radiographic-pathologic correlation in bronchopulmonary dysplasia. J Pediatr 95: 834–836.
Henry J. Rozycki 1994 Bronchoalveolar interleukin-1 in infants on day 1 of life. South Med J 87: 991–996.
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.
Bagchi A, Viscardi RM, Taciak V, Ensor JE, McCrea KA, Hasday JD 1994 Increased activity of interleukin-6 but not tumor necrosis factor- in lung lavage of premature infants is associated with the development of bronchopulmonary dysplasia. Pediatric Res 36: 2:244-252
Yeh TF, Torre JA, Rastogi A, Anyebuno MA, Pildes RS 1990 Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome; a double-blind, controlled study. J Pediatr 117: 273–282.
Murch SH, McDonald TT, Wood CB, Costeloe KL 1992 Tumor necrosis factor in the bronchoalveolar secretions of infants with the respiratory distress syndrome and the effect of dexamethasone treatment. Thorax 47: 44–47.
Danders RJ, Cox C, Phelps DL, Sinkin RA 1994 Two doses of early intravenous dexamethasone for the prevention of bronchopulmonary dysplasia in babies with respiratory distress syndrome. Pediatr Res 36: 122–128.
Beutler B, Cerami A 1986 Cachectintumor necrosis factor: an andogenous mediator of shock and inflammation. Immunol Res 5: 281–293.
Old LJ 1985 Tumor necrosis factor (TNF). Science 230: 630–632.
Stephens KE, Ishizaka A, Larrick JW, Raffin TA 1988 Tumor necrosis factor causes increased pulmonary permeability and edema. Am Rev Respir Dis 137: 1364–1370.
Kownatzki E, Kapp A, Uhrich S 1988 Modulation of human neutrophic granulocyte functions by recombinant human tumor necrosis factor and recombinant human lymphotoxin. Promotion of adherence, inhibition of chemotactic migration and superoxide anion release from adherent cells. Clin Exp Immunol 74: 143–148.
Ozaki Y, Ohashi T, Niwa Y, Kume S 1988 Effect of recombinant DNA-produced tumor necrosis factor on various parameters of neutrophil function. Inflammation 12: 297–300.
Oppenheim JJ, Kovacs EJ, Matsushima K, Durum SK 1986 There is more than one interleukin 1. Immunol Today 7: 45–56.
Pahlman TH, Stanness KA, Beatty PG, Ochs HK, Harlan JM 1986 An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin-1, and tumor necrosis factor increases neutrophil adherence by a Cdw18 (LFA)-dependent mechanism. J Immunol 136: 4548–4553.
Ruber JS, Lapierre LA, Stolpen AH, Brock TA, Springer TA, Fiets W, Bevilacqua MP, Mendrick DL, Gimbrone MA Jr 1987 Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin 1 species. J Immunol 138: 3319–3324.
Breviario F, Bertocchi F, Dejana E, Bussolino F 1988 IL-1 induced adhesion of polymorphonuclear leukocytes to cultured human endothelial cells. J Immunol 141: 3391–3397.
Moser RB, Schleiffenbaum P, Groscurth P, Fehr J 1989 Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 83: 444–455.
Matsushima K, Oppenheim JJ 1989 Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL-1 and TNF. Cytokine 1: 2–13.
Baggiolini M, Walz A, Kunkel SL 1989 Neutrophil activating peptide-1/interleukin 8, a novel cytokine that activates netrophils. J Clin Invest 84: 1045–1049.
Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ 1987 Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokine. Proc Natl Acad Sci USA 84: 9233–9237.
Van Zee KJ, DeForge LE, Fischer E, Marano MA, Kenney JS, Remick DG, Lowry SF, Moldawer LL 1991 IL-8 in septic shock, endotoxemia, and following IL-1 administration. J Immunol 146: 3478–3482.
de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE 1991 Interleukin-10 (IL-10) inhibits cytokine synthesis by human monocytes. An autoregulatory role of IL-10 produced by monocytes. J Exp Med 174: 1209–1220.
Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A 1991 IL-10 inhibits cytokine production by activated macrophages. J Immunol 147: 3815–3822.
Spits H, de Waal Malefyt R 1992 Functional characterization of human IL-10. Int Arch Allergy Immunol 99: 8–15.
Howard M, O'Garra A, Ishida H, de Waal MR, deVries J 1992 Biological properties of interleukin 10. J Clin Immunol 12: 239–247.
Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O'Garra A 1991 IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th-1 cells. J Immunol 146: 3444–3451.
Bryson YJ, Winter HS, Gard SE, Fischer TJ, Stiehm ER 1980 Deficiency of immune interferon production by leukocytes of normal newborns. Cell Immunol 55: 191–200.
Lewis DB, Prickett K, Larson A, Grabstein K, Weaver M, Wilson CB 1988 Restricted production of interleukin 4 by activated human T cells. Proc Natl Acad Sci USA 85: 9743–9747.
Seki H, Taga K, Matsuda A, Uwadana N, Hasul M, Miyawaki T, Tangiguchi N 1986 Phenotypic and functional characteristics of active suppressor cells against IFN- production in PHA-stimulated cord blood lymphocytes. J Immunol 137: 3158–3161.
Lewis DB, Larsen A, Wilson CB 1986 Reduced interferon-γ mRNA levels in human neonates. Evidence for an instrinsic T cell deficiency independent of other gene involved in T cell activation. J Exp Med 163: 1018–1023.
English BK, Hammond WP, Lewis DB, Brown CB, Wilson CB 1991 Decreased granulocyte-macrophage colony-stimulating factor production by human neonatal blood mononuclear cells and T cells. Pediatr Res 31: 211–216.
NHLBI Workshop Summary 1993 Assessment of lung function and dysfunction in studies of infants and children. Am Rev Respir Dis 148: 1105–1108.
Hillier SL, Witkin SS, Krohn MA, Watts DH, Kiviat NB, Eschenbach DA 1993 The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol 81: 941–948.
Chheda S, Palkowetz KH, Garofalo R, Rassin DK, Goldman AS 1995 Developmental delay in the production of IL-10 by human neonatal blood monocytes and T cells. Pediatr Res 37( suppl 2: 280A( abstr.)
Schibler KR, Le TV, Carroll WL 1995 Mechanisms accounting for diminished interleukin-10 gene expression in human blood mononuclear cells. Pediatric Res 37( suppl 2): 285A( abstr.)
Wanidworanun C, Strober W 1993 Predominant role of tumor necrosis factor-α in human monocyte IL-10 synthesis. J Immunol 151: 6853–6861.
Barnes PJ 1994 Appreciating the role of airway inflammation in asthma. J Respir Dis 15: 5S7-S18
Khalil N, Bereznay O, Sporn M, Greenberg AH 1989 Macrophage product of transforming growth factor β and fibroblast collagen synthesis chronic pulmonary inflammation. J Exp Med 170: 727–737.
Broekelmann TJ, Limper AH, Colby TV, McDonald JA 1991 Transfer growth factor β, is present at sites of extracellular matrix expression human pulmonary fibrosis. Proc Natl Acad Sci USA 88: 6642–6646.
Khalil N, O'Connor RN, Unruh HW, Warren PW, Flanders KC 1991 Increased production and immunohistochemical localization of transforming growth factor in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 5: 155–162.
Martinet Y, Rom WN, Grotendorst GR, Martin GR, Crystal RG 1987 Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis. N Engl J Med 317: 202–209.
Antoniades HN, Bravo MA, Avila RE 1990 Platelet-derived growth factor in idiopathic pulmonary fibrosis. J Clin Invest 86: 1055–1064.
Snyder LS, Hertz MI, Peterson MS 1991 Acute lung injury pathogenesis of intraveolar fibrosis. J Clin Invest 88: 663–667.
Acknowledgements
The authors thank Dr. Florence Hofman and her laboratory for assistance with this work as well as Donna Cho for excellent secretarial services. We also thank the Nursing and Respiratory Therapy staff of the Neonatal Intensive Care Unit at Women's & Children's Hospital for their help in obtaining the BAL samples.
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Supported in part by National Institutes of Health Grant HL 48298 and by the Hastings Foundation.
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Jones, C., Cayabyab, R., Kwong, K. et al. 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 (1996). https://doi.org/10.1203/00006450-199606000-00007
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DOI: https://doi.org/10.1203/00006450-199606000-00007
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