Abstract
During the course of human pregnancy, glucocorticoid (GC) treatment is given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, in animal studies, a number of side effects of perinatal GC treatment have been described. The aim of the present study was to evaluate in humans the effects of antenatal GC treatment on development of the immune system. In addition, we examined the development of immune reactivity in infants born preterm and at term who did not receive GC treatment antenatally. We tested mitogen-induced T cell proliferation, natural killer cell activity, and lipopolysaccharide-induced IL-6 production in cord blood samples. We found that there is a significant effect of gestational age on the capacity of T cells to proliferate and of natural killer cells to kill K562 tumor cells. The capacity to produce IL-6 does not change between gestational age 26 and 41 wk. Moreover, our results show that antenatal treatment with GC does have immunomodulatory effects: T cell proliferation is decreased in infants born very preterm (gestational age 26-31 wk) as well as in infants born between 32 and 36 wk of gestation. In contrast, the activity of natural killer cells is only increased in GC-treated infants born between 26 and 31 wk. We did not observe a significant effect of antenatal GC treatment on the capacity to produce IL-6.
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Abbreviations
- GC :
-
glucocorticoids
- NK :
-
natural killer
- PHA :
-
phytohemagglutinin
- LPS :
-
lipopolysaccharide
- SGA :
-
small for gestational age
- LGA :
-
large for gestational age
- AGA :
-
appropriate for gestational age
References
Liggins G, Howie R 1972 Prevention of respiratory distress syndrome in premature infants by antepartum glucocorticoid treatment. Pediatrics 50: 515–525.
Crowley P, Chalmers I, Keirse MJNC 1990 The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 97: 11–25.
Crowley PA 1995 Antenatal corticosteroid therapy: a meta-analysis of the trials, 1972 to 1995. Am J Obstet Gynecol 173: 322–334.
De Kloet ER, Rosenfeld P, Van Eekelen JAM, Sutanto W, Levine S 1988 Stress, glucocorticoids, and development. In: Boer GJ, Feenstra MGP, Mirmiran M, Swaab DF, Van Haaren F (eds) Progress in Brain Research, Vol. 73. Elsevier Science Publishers, Amsterdam, 101–120.
Bian X, Seidler FJ, Slotkin TA 1993 Fetal DEX exposure interferes with establishment of cardiac noradrenergic innervation and sympathetic activity. Teratology 47: 109–117.
Derks JB, Mulder EJH, Visser GHA 1995 The effects of maternal betamethasone administration on the fetus. Br J Obstet Gynaecol 102: 40–46.
Schmand B, Neuvel J, Smolders-De Haas H, Hoeks J, Treffers PE, Koppe JG 1990 Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 86: 58–64.
Smolders-De Haas H, Neuvel J, Schmand B, Treffers PE, Koppe JG, Hoeks J 1990 Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: 10-12 year follow-up. Pediatrics 86: 65–70.
Cote JC, Meuwissen HJ, Pickering RJ 1974 Effects on neonate of prednisone and azathioprine administered to mother during pregnancy. J Pediatr 85: 324–328.
Eishi Y, Hirokawa K, Hatakeyama S 1983 Long-lasting impairment of immune and endocrine systems of offspring induced by injection of dexamethasone into pregnant mice. Clin Immunol Pathol 26: 335–349.
Levine Ross J, Schulte HM, Galucci WT, Cutler GBJ, Loriaux DL, Chrousos GP 1986 Ovine corticotropin-releasing hormone stimulation test in normal children. J Clin Endocrinol Metab 62: 390–392.
Bakker JM, Donne-Smidt E, Kavelaars A, Heijnen CJ, Tildres FJH, Van Rees EP 1995 Effects of short-term dexamethasone treatment during pregnancy on the development of the immune system and the hypothalamo-pituitary adrenal axis in the rat. J Neuroimmunol 63: 183–192.
Bakker JM, Donne Schmidt E, Kroes H, Kavelaars A, Heijnen CJ, Tilders FJH, Van Rees EH 1997 Effects of neonatal dexamethasone treatment on hypothalamo-pituitary-adrenal axis and immune system of the rat. J Neuroimmunol 74: 69–76.
Lew W, Oppenheim JJ, Matsushima K 1988 Analysis of the suppression of IL-1 alpha and IL-1 beta production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J Immunol 140: 1895–1902.
Waage A, Slupphag G, Shalaby R 1990 Glucocorticoids inhibit the production of interleukin-6 from monocytes, endothelial cells, and fibroblasts. Eur J Immunol 20: 2439–2443.
Gillis S, Wong-Staal F, Crabtree GR, Smith KA 1994 Glucocorticoid-induced inhibition of T cell growth factor production. I. The effects on mitogen-induced lymphocyte proliferation. J Immunol 123: 1624–1629.
Wyllie AH 1979 Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. J Immunol 123: 1624–1631.
Kavelaars A, Cats B, Visser GHA, Zegers BJM, Bakker JM, Van Rees EP, Heijnen CJ 1996 Ontogeny of the response of human peripheral blood T cells to glucocorticoids. Brain Behav Immun 10: 288–297.
Kavelaars A, Zijlstra J, Bakker JM, Van Rees EP, Visser GHA, Zegers BJM, Heijnen CJ 1995 Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells. Eur J Immunol 25: 1346–1351.
Hand DJ, Taylor CC 1993 Multivariate Analysis of Variance and Repeated Measures. A Practical Approach for Behavioural Scientists. Chapman & Hall, London, 109–145.
Liggins GC 1994 The role of cortisol in preparing the fetus for birth. Reprod Fert Dev 61: 141–150.
Barnes P, Jacobs M, Roberts JM 1984 Glucocorticoids preferentially increase fetal alveolar -adrenoreceptors: autoradiographic evidence. Pediatr Res 18: 1191–1194.
Schedlowski M, Jacobs R, Stratmann G, Richter S, Hadicke A, Tewes U, Wagner TOF, Schmidt RE 1993 Changes of natural killer cells during acute psychological stress. J Clin Immunol 13: 118–126.
Benschop RJ, Oostveen FG, Heijnen CJ, Ballieux RE 1993 Beta 2-adrenergic stimulation causes detachment of natural killer cells from cultured endothelium. Eur J Immunol 23: 3242–3247.
Murthy KK, Moya FR 1994 Effect of betamethasone on maternal, fetal, and neonatal rat cellular immunity. Early Hum Dev 36: 1–11.
Cupps TR, Fauci AS 1982 Corticosteroid-mediated immunoregulation in man. Immunol Rev 65: 133–155.
Waage A, Bakke O 1988 Glucocorticoids suppress the production of tumor necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunol 63: 299–302.
Paliogianni F, Raptos A, Ahuja SS, Najjar SM, Boumpas DT 1993 Negative transcriptional regulation of human interleukin 2 (IL-2) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT. J Clin Invest 91: 1481–1489.
Northrop JP, Crabtree GR, Mattila PS 1992 Negative regulation of interleukin-2 transcription by the glucocorticoid receptor. J Exp Med 1755: 1235–1245.
Lew W, Oppenheim JJ, Matsushima K 1988 Analysis of the suppression of IL-1 and IL-1 production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J Immunol 140: 1892–1902.
Acknowledgements
The authors thank Jitske Zijlstra, Anita Meijer, and Ilse de Koe for excellent technical assistance. We also thank Dr. J.A.J. Faber for biostatistical advice and the nursing staff of the Department of Obstetrics of the Academic Hospital, Utrecht, for impressive support.
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Supported by “Het Praeventiefonds” grants 28-2198 and 28-2197.
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Kavelaars, A., van der Pompe, G., Bakker, J. et al. Altered Immune Function in Human Newborns after Prenatal Administration of Betamethasone: Enhanced Natural Killer Cell Activity and Decreased T Cell Proliferation in Cord Blood. Pediatr Res 45, 306–312 (1999). https://doi.org/10.1203/00006450-199903000-00003
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DOI: https://doi.org/10.1203/00006450-199903000-00003
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