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Klin Padiatr 2017; 229(05): 261-266
DOI: 10.1055/s-0043-114666
Review
© Georg Thieme Verlag KG Stuttgart · New York

Endocrine Factors Determining Immune Polarization during Perinatal Transition

Endokrine Faktoren und Immunpolarisierung während der perinatalen Adaptationsperiode
Barna Vásárhelyi
1   Semmelweis Egyetem, Department of Laboratory Medicine, Budapest, Hungary
,
Tivadar Tulassay
2   Semmelweis Egyetem, Ist Department of Pediatrics, Budapest, Hungary
› Author Affiliations
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Publication History

Publication Date:
26 July 2017 (online)

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Abstract

In utero the skewness of the adaptive immune system towards Th2 (‘antiinflammatory’) direction and low of Th1/Th2 cell ratio defend the fetus against rejection by the maternal immune system. Th2 dominance at birth is also of importance as it prevents uncontrolled inflammatory processes during parturition. This condition should change rapidly after birth. In an extrauterine milieu that is inherent with exposure to microorganisms, Th1 (‘proinflammatory’) polarization (i. e. increased Th1 cytokine production along with high Th1/Th2 ratio) are required to maintain an efficient immune response. After birth, maternal hormone supplies including estrogen, progesterone, testosterone, and antiinflammatory prostaglandins cease abruptly. As these hormones have an immune modulatory action favoring Th2, and inhibiting Th1 polarization, their low level supports the strengthening of Th1-type immunity. During parturition a dramatic but transient increase of several hormones (oxytocin, thyorid hormones, and catecholamines) occurs. Again, the net effect of high hormone levels favors Th2 activation, followed by Th1 polarization when hormonal levels reach their postnatal levels. The perinatal change of these components results in the quick cessation of Th1 inhibition and supports the maturation of adaptive immunity to provide an effective response against extrauterine microorganisms.

Zusammenfassung

Der Fötus wird im intrauterinen Leben durch die Th2-(antiinflammatorische) Polarisierung des adaptiven Immunsystems und die Verminderung des Th1/Th2-Verhältnisses vor der Rejektion des maternalen Immunsystems geschützt. Die Th2 Dominanz ist dabei bei der Geburt besonders wichtig, da sie einen nicht-kontrollierten Entzündungsprozess verhindert. Kurz nach der Geburt ändert sich diese Konstellation. Im extrauterinen Milieu wird die effektive Immunantwort durch die Th1 Polarisierung (d. h. erhöhte Produktion Th1 Zytokine und eine Verschiebung des Th1/Th2 Verhältnisses) ermöglicht. Während der Geburt werden transitorisch einige Hormone (z. B. Oxytocin, Thyroid Hormone, Katecholamine) in Exzess produziert. Die mütterliche, Th2-fördernde Hormon-Versorgung (z. B. Oestrogen, Progesterone, Testosterone, anti-inflammatorische Prostaglandine) lässt unmittelbar nach der Geburt nach. Sobald die Hormonspiegel das postnatale Niveau erreichen, haben diese Prozesse eine Th2-Aktivation gefolgt von einer Th1 Polarisierung zur Folge. Die perinatale Adaptation führt dann zu einem schnellen Ende der Th1 Inhibition und unterstützt die Reifung der adaptiven Immunität, die einen wirksamen Schutz gegen extrauterine Mikroorganismen ermöglicht.

Key words

immune system - perinatal adaptation - Th1/Th2 polarization - endocrine systems

Schlüsselwörter

perinatale Adaptation - Immunsystem - Th1/Th2-Verhältniss - endokrine Regulation
 

  • References

  • 1 Adkins B. T-cell function in newborn mice and humans. Immunol Today 1999; 20: 330-335
    CrossrefPubMedGoogle Scholar
  • 2 Basha S, Surendran N, Pichichero M. Immune responses in neonates. Expert Rev Clin Immunol 2014; 10: 1171-1184
    CrossrefPubMedGoogle Scholar
  • 3 Conly PW, Morrison T, Sandberg DH. et al. Concentrations of progesterone in the plasma of mothers and infants at time of birth. Pediatr Res 1970; 4: 76-81
    CrossrefPubMedGoogle Scholar
  • 4 Debock I, Flamand V. Unbalanced neonatal CD4(+) T-cell immunity. Front Immunol 2014; 5: 393
    PubMedGoogle Scholar
  • 5 Doria A, Iaccarino L, Arienti S. et al. Th2 immune deviation induced by pregnancy: the two faces of autoimmune rheumatic diseases. Reprod Toxicol 2006; 22: 234-241
    CrossrefPubMedGoogle Scholar
  • 6 Doria A, Iaccarino L, Sarzi-Puttini P. et al. Estrogens in pregnancy and systemic lupus erythematosus. Ann. N. Y. Acad. Sci 2006; 1069: 247-256
    CrossrefPubMedGoogle Scholar
  • 7 Fan X, Wang Y. β2 Adrenergic receptor on T lymphocytes and its clinical implications. Progress in Natural Science 2009; 19: 17-23
    CrossrefPubMedGoogle Scholar
  • 8 Garcia AM, Fadel SA, Cao S. et al. T cell immunity in neonates. Immunol Res 2000; 22: 177-190
    CrossrefPubMedGoogle Scholar
  • 9 Heckmann M, Hartmann MF, Kampschulte B. et al. Persistent high activity of the fetal adrenal cortex in preterm infants: is there a clinical significance?. J Pediatr Endocrinol Metab 2006; 19: 1303-1312
    PubMedGoogle Scholar
  • 10 Hillman NH, Kallapur SG, Jobe AH. Physiology of transition from intrauterine to extrauterine life. Clin Perinatol 2012; 39: 769-783
    CrossrefPubMedGoogle Scholar
  • 11 Hodkinson CF, Simpson EE, Beattie JH. et al. Preliminary evidence of immune function modulation by thyroid hormones in healthy men and women aged 55-70 years. J Endocrinol 2009; 202: 55-63
    CrossrefPubMedGoogle Scholar
  • 12 Huang MT, Yang YH, Lin YT. et al. Beta2-agonist exerts differential effects on the development of cord blood T cells but not on peripheral blood T cells. Pediatr Allergy Immunol 2001; 12: 17-20
    CrossrefPubMedGoogle Scholar
  • 13 Hübner S, Sunny DE, Pöhlke C. et al. Protective effects of fetal zone steroids are comparable to estradiol in hyperoxia-induced cell death of immature glia. Endocrinology 2017; 158: 1419-1435
    CrossrefPubMedGoogle Scholar
  • 14 Johnson HM, Torres BA. Regulation of lymphokine production by arginine vasopressin and oxytocin: modulation of lymphocyte function by neurohypophyseal hormones. J Immunol 1985; 135: 773-775
    PubMedGoogle Scholar
  • 15 Kalinski P. Prostaglandin E regulation of immune responses. J Immunol 2012; 188: 21-28
    CrossrefPubMedGoogle Scholar
  • 16 Kissick HT, Sanda MG, Dunn LK. et al. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci USA 2014; 111: 9887-9892
    CrossrefPubMedGoogle Scholar
  • 17 Liberman AC, Druker J, Refojo D. et al. Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells. FASEB J 2009; 23: 1558-1571
    CrossrefPubMedGoogle Scholar
  • 18 Lissauer D, Eldershaw SA, Inman CF. et al. Progesterone promotes maternal–fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile. Eur J Immunol 2015; 45: 2858-2872
    CrossrefPubMedGoogle Scholar
  • 19 Macciò A, Madeddu C, Chessa P. et al. Oxytocin both increases proliferative response of peripheral blood lymphomonocytes to phytohemagglutinin and reverses immunosuppressive estrogen activity. In Vivo 2010; 24: 157-163
    PubMedGoogle Scholar
  • 20 Makieva S, Saunders PT, Norman JE. Androgens in pregnancy: roles in parturition. Hum Reprod Update 2014; 20: 542-559
    CrossrefPubMedGoogle Scholar
  • 21 Märker-Hermann E, Fischer-Betz R. Rheumatic diseases and pregnancy. Curr. Opin. Obstet. Gynecol 2010; 22: 458- 465
    CrossrefPubMedGoogle Scholar
  • 22 Marodi L. Down-regulation of Th1 responses in human neonates. Clin Exp Immunol 2002; 128: 1-2
    CrossrefPubMedGoogle Scholar
  • 23 Melville JM, Moss TJ. The immune consequences of preterm birth. Front Neurosci 2013; 7: 79
    CrossrefPubMedGoogle Scholar
  • 24 Midgley PC, Russell K, Oates N. et al. Activity of the adrenal fetal zone in preterm infants continues to term. Endocr Res 1996; 22: 729-733
    CrossrefPubMedGoogle Scholar
  • 25 Miller VM, Duckles SP. Vascular actions of estrogens: functional implications. Pharmacological Reviews 2008; 60: 210-241
    CrossrefPubMedGoogle Scholar
  • 26 Morel Y, Roucher F, Plotton I. et al. Evolution of steroids during pregnancy: Maternal, placental and fetal synthesis. Ann Endocrinol 2016; 77: 82-89
    CrossrefPubMedGoogle Scholar
  • 27 Nuriel-Ohayon M, Neuman H, Koren O. Microbial changes during pregnancy, birth, and infancy. Front Microbiol 2016; 7: 1031
    PubMedGoogle Scholar
  • 28 Polese B, Gridelet V, Araklioti E. et al. The endocrine milieu and CD4 T-lymphocyte polarization during pregnancy. Front Endocrinol (Lausanne) 2014; 5: 106
    PubMedGoogle Scholar
  • 29 Prabhu SB, Rathore DK, Nair D. et al. Comparison of human neonatal and adult blood leukocyte subset composition phenotypes. PLoS One 2016; 11: e0162242
    CrossrefPubMedGoogle Scholar
  • 30 Robinson DP, Klein SL. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm Behav 2012; 62: 263-271
    CrossrefPubMedGoogle Scholar
  • 31 Romero R, Savasan ZA, Chaiworapongsa T. et al. Hematologic profile of the fetus with systemic inflammatory response syndrome. J. Perinat. Med 2011; 40: 19-32
    PubMedGoogle Scholar
  • 32 Saito S, Nakashima A, Shima T. et al. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010; 63: 601-610
    CrossrefPubMedGoogle Scholar
  • 33 Sanders VM. Adrenergic receptors on T and B lymphocytes: Evidence, function, and clinical implications. Clinical Neuroscience Research 2006; 6: 34-41
    CrossrefPubMedGoogle Scholar
  • 34 Schumacher A, Costa SD, Zenclussen AC. Endocrine factors modulating immune responses in pregnancy. Front Immunol 2014; 5: 196
    PubMedGoogle Scholar
  • 35 Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci 2015; 282: 20143085
    CrossrefPubMedGoogle Scholar
  • 36 Straub RH. The complex role of estrogens in inflammation. Endocr Rev 2007; 28: 521-574
    CrossrefPubMedGoogle Scholar
  • 37 Sykes L, MacIntyre DA, Teoh TG. et al. Anti-inflammatory prostaglandins for the prevention of preterm labour. Reproduction 2014; 148: R29-R40
    CrossrefPubMedGoogle Scholar
  • 38 Szathmári M, Vásárhelyi B, Tulassay T. Effect of low birth weight on adrenal steroids and carbohydrate metabolism in early adulthood. Horm Res 2001; 55: 172-178
    CrossrefPubMedGoogle Scholar
  • 39 Szekeres-Bartho J. Immunological relationship between the mother and the fetus. Int Rev Immunol 2002; 21: 471-495
    CrossrefPubMedGoogle Scholar
  • 40 Szekeres-Bartho J, Polgar B. PIBF: the double edged sword. Pregnancy and tumor. Am J Reprod Immunol 2010; 64: 77-86
    PubMedGoogle Scholar
  • 41 Toldi G, Saito S, Shima T. et al. The frequency of peripheral blood CD4+ CD25high FoxP3+ and CD4+ CD25- FoxP3+ regulatory T cells in normal pregnancy and pre-eclampsia. Am J Reprod Immunol 2012; 68: 175-180
    CrossrefPubMedGoogle Scholar
  • 42 Toldi G, Stenczer B, Treszl A. et al. Lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in healthy pregnancy and preeclampsia. Am J Reprod Immunol 2011; 65: 154-163
    CrossrefPubMedGoogle Scholar
  • 43 Toldi G, Treszl A, Pongor V. et al. T-lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in the neonate. Int Immunol 2010; 22: 769-774
    CrossrefPubMedGoogle Scholar
  • 44 Toldi G, Vásárhelyi ZE, Rigó J. et al. Prevalence of regulatory T-cell subtypes in preeclampsia. Am J Reprod Immunol 2015; 74: 110-115
    CrossrefPubMedGoogle Scholar
  • 45 Trotter A, Maier L, Grill HJ. et al. Effects of postnatal estradiol and progesterone replacement in extremely preterm infants. J Clin Endocrinol Metab 1999; 84: 4531-4535
    CrossrefPubMedGoogle Scholar
  • 46 Trotter A, Maier L, Kron M. et al. Effect of oestradiol and progesterone replacement on bronchopulmonary dysplasia in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed 2007; 92: F94-F98
    CrossrefPubMedGoogle Scholar
  • 47 Trotter A, Steinmacher J, Kron M. et al. Neurodevelopmental follow-up at five years corrected age of extremely low birth weight infants after postnatal replacement of 17β-estradiol and progesterone. J Clin Endocrinol Metab 2012; 97: 1041-1047
    CrossrefPubMedGoogle Scholar
  • 48 Uvnäs-Moberg K, Widström AM, Werner S. et al. Oxytocin and prolactin levels in breast-feeding women. Correlation with milk yield and duration of breast-feeding. Acta Obstet Gynecol Scand 1990; 69: 301-306
    CrossrefPubMedGoogle Scholar
  • 49 Vargas-Rojas MI, Solleiro-Villavicencio H, Soto-Vega E. Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia. J Matern Fetal Neonatal Med 2016; 29: 1642-1645
    CrossrefPubMedGoogle Scholar
  • 50 Vásárhelyi B, Mészáros K, Karvaly G. et al. Focusing on tissue biomarkers. Estrogens as key players in the modulation of immune response and autoimmunity. Orv Hetil 2015; 156: 2070-2076
    CrossrefPubMedGoogle Scholar
  • 51 Wegmann TG, Lin H, Guilbert L. et al. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?. Immunology Today 1993; 7: 353-356
    PubMedGoogle Scholar
  • 52 Zaghouani H, Hoeman CM, Adkins B. Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends in Immunology 2009; 30: 585-591
    CrossrefPubMedGoogle Scholar