Schizophrenia Research
Volume 47, Issue 1 , Pages 27-36 , 15 January 2001

Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain

  • Ari Urakubo

      Affiliations

    • Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
    • ,
  • L.Fredrik Jarskog

      Affiliations

    • Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
    • UNC Mental Health and Neuroscience Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
    • ,
  • Jeffrey A. Lieberman
    • ,
  • John H. Gilmore

      Affiliations

    • Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
    • UNC Mental Health and Neuroscience Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
    • Corresponding Author InformationCorresponding author. Present address: Department of Psychiatry, CB# 7160, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA. Tel.: +1-919-966-6971; fax: +1-919-966-7659

Received 3 September 1999 ,Accepted 24 January 2000.

References 

  1. Abbas AK, Lichtman AH, Pober JS. Cellular and Molecular Immunology. Philadelphia: W.B. Saunders; 1994;
  2. Adinolfi M. Infectious diseases in pregnancy, cytokines and neurological impairment: an hypothesis. Dev. Med. Child. Neurol. 1993;35:549–553
  3. Andrews WW, Hauth JC, Goldenberg RL, Gomez R, Romero R, Cassell GH. Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women who delivers after spontaneous labor versus indicated delivery. Am. J. Obstet. Gynecol. 1995;172:606–612
  4. Arajujo DM, Cotman CW. Differential effects of interleukin-1b and interleukin-2 on glia and hippocampal neurons in culture. Int. J. Dev. Neurosci. 1995;13:201–212
  5. Arntzen KJ, Kjollesdal AM, Halgunset J, Vatten L, Austgulen R. TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. J. Perinat. Med. 1998;26:17–26
  6. Beckmann I, Meisel-Mikolajczyk F, Leszczynski P, Brooijmans M, Wallenburg HCS. Endotoxin-induced fetal growth retardation in the pregnant guinea pig. Am. J. Obstet. Gynecol. 1993;168:714–718
  7. Bickel U, Grave B, Kang YS, del Ray A, Voigt K. No increase in blood-brain- barrier permeability after intraperitoneal injection of endotoxin in the rat. J. Neuroimmunol. 1998;85:131–136
  8. Bredow S, Guha-Thakurta N, Taishi P, Obal F, Kreuger JM. Diurnal variations of tumor necrosis facto alpha mRNA and alpha-tubulin mRNA in rat brain. Neuroimmunomodulation. 1997;4(2):84–90
  9. Brown AS, Schaefer CA, Wyatt RJ, Goetz R, Begg M, Susser ES. Prenatal exposure to respiratory and genital/reproductive infections and adult schizophrenia spectrum disorders: a prospective birth cohort study. Schizophr. Bull. 2000;in press
  10. Buchanan RW, Vladar K, Barta PE, Pearlson GD. Structural evaluation of the prefrontal cortex in schizophrenia. Am. J. Psychiatry. 1998;155:1049–1055
  11. Carbo N, Lopez-Soriano FJ, Argiles JM. Tumor necrosis factor-alpha does not cross the rat placenta. Cancer Lett. 1998;128(1):101–104
  12. Chao CC, Hu S. Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cultures. Dev. Neurosci. 1994;16:171–179
  13. Collins JG, Smith MA, Arnold RR, Offenbacher S. Effects of escherichia coli and porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster. Infect. Immun. 1994;62:4652–4655
  14. Dalman C, Allebeck P, Cullberg J, Grunewald C, Koster M. Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort. Arch. Gen. Psychiatry. 1999;56(3):234–240
  15. Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr. Res. 1997;42:1–8
  16. Dammann O, Leviton A. Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant. Sem. Ped. Neurol. 1998;5:190–201
  17. Deguchi K, Mizuguchi M, Takashima S. Immunohistochemical expression of tumor necrosis factor α in neonatal leukomalacia. Pediatr. Neurol. 1996;14:13–16
  18. Fidel PL, Romero R, Wolf N, Cutright J, Ramirez M, Araneda H, et al. Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice. Am. J. Obstet. Gynecol. 1994;170:1467–1475
  19. Floyd RA, Krueger JM. Diurnal variation of TNF alpha in the rat brain. Neuroreport. 1997;8(4):915–918
  20. Fortunato SJ, Menon RP, Swan KF, Menon R. Inflammatory cytokine (interleukins 1,6,8 and tumor necrosis factor-α) release from cultured fetal membranes in response to endotoxic lipoplysaccharide mirrors amniotic fluid concentrations. Am. J. Obstet. Gynecol. 1996;174:1855–1862
  21. Gatti S, Bartfai T. Induction of tumor necrosis factor-α mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6. Brain Res. 1993;624:291–294
  22. Geddes JR, Lawrie SM. Obstetric complication and schizophrenia: a meta-analysis. Br. J. Psychiatry. 1995;167:786–793
  23. Gibbs RS, Romero R, Hillie SL, Eschenbach DA, Sweet RL. A review of premature birth and subclinical infection. Am. J. Obstet. Gynecol. 1992;166:1515–1528
  24. Gilmore JH, Castillo M, Rojas M. Early onset schizophrenia in a patient with premature birth, germinal matrix hemorrhage and periventricular leukomalacia. Schizophr. Res. 1999;in press
  25. Gilmore JH, Jarskog LF. Exposure to infection and brain development: cytokines in the pathogenesis of schizophrenia. Schizophr. Res. 1997;24:365–367
  26. Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am. J. Obstet. Gynecol. 1998;179:194–202
  27. Goto M, Yoshioka T, Ravindranath T, Battelino T, Young RI, Zeller MP. LPS injected into the pregnant rat late in gestation does not induce fetal endotoxemia. Res. Comm. Mol. Path. Pharm. 1994;85:109–112
  28. Goujon E, Parnet P, Laye S, Combe C, Dantzer R. Adrenalectomy enhances pro-inflammatory cytokines gene expression in the spleen, pituitary and brain of mice in response to lipopolysaccharide. Mol. Brain Res. 1996;36:53–62
  29. Greci LS, Gilson GJ, Nevils R, Izquierdo LA, Qualls CA, Curet LB. Is amniotic fluid analysis the key to preterm labor? A model using interleukin-6 for predicting rapid delivery. Am. J. Obstet. Gynecol. 1998;179:172–178
  30. Greig PC, Ernest JM, Teot L, Erikson M, Talley R. Amniotic fluid interleukin-6 levels correlate with histologic chorioamniotis and amniotic fluid cultures in patients in premature labor with intact membranes. Am. J. Obstet. Gynecol. 1993;169:1035–1044
  31. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. J. Am. Med. Assoc. 1997;278:207–211
  32. Hesse K, Hock C, Otten U. Inflammatory signals induce neurotrophin expression in human microglia cells. J. Neurochem. 1998;70:699–707
  33. Hirsch E, Blanchard R, Mehta SP. Differential fetal and maternal contributions to the cytokine milieu in a murine model of infection-induced preterm birth. Am. J. Obstet Gynecol. 1999;180:429–434
  34. Hsu CD, Witter FR. Urogenital infection in preeclampsia. Int. J. Gynaecol. Obstet. 1995;49(3):271–275
  35. Hultman CM, Sparen P, Takei N, Murray RM, Cnattingius S. Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive n psychosis of early onset: case–control study. Br. Med. J. 1999;318:421–426
  36. Jarskog LF, Xiao H, Wilkie MB, Lauder JM, Gilmore JH. Cytokine regulation of fetal dopaminergic and serotonergic neuron survival in vitro. Int. J. Dev. Neurosci. 1997;15:711–716
  37. Jones PB, Rantakallio P, Hartikainen A, Isohanni M, Sipila P. Schizophrenia as a long term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 North Finland general population birth cohort. Am. J. Psychiatry. 1998;155:355–364
  38. Kendall RE, Juszczcak E, Cole SK. Obstetrical complications and schizophrenia: a case control study based on standardized obstetric records. Br. J. Psychiatry. 1998;168:556–561
  39. Kent AS, Sullivan MH, Elder MG. Transfer of cytokines through human fetal membranes. J. Reprod. Fertil. 1994;100:81–84
  40. Letterio JJ, Geiser AG, Kulkarni AB, Roche NS, Sporn MB, Roberts AB. Maternal rescue of transforming growth factor-β1 null mice. Science. 1994;264:36–38
  41. Leviton A. Preterm birth and cerebral palsy: is tumor necrosis factor the missing link?. Dev. Med. Child. Neurol. 1993;35:553–558
  42. Lim KO, Hedehus M, Moseley M, de Crispigny A, Sullivan EV, Pfefferbaum A. Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. Arch. Gen. Psychiatry. 1999;56:367–374
  43. Marx CE, Vance BJ, Jarskog LF, Chescheir NC, Gilmore JH. Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 levels in human amniotic fluid. Am. J. Obstet. Gynecol. 1999;181:1125–1230
  44. Mayhan WG. Effect of lipopolysaccharide on the permeability and reactivity of the cerebral microcirculation: role of inducible nitric oxide synthase. Brain Res. 1998;792:353–357
  45. McGrath J, Murry R. Risk factors for schizophrenia. In:  Hirsh SR,  Weinberger DR editor. Schizophrenia. Cambridge, MA: Blackwell Science; 1995;p. 196–199
  46. Medlock ES, Kaplan DL, Cecchini M, Ulich TR, del Castillo J, Andersen J. Granulocyte-stimulating factor crosses the placenta and stimulates fetal granulopoeisis. Blood. 1993;81:916–922
  47. Mehler MF, Marmur R, Gross P, Mabie PC, Zang Z, Papavasiliou A, et al. Cytokines regulate the cellular phenotype of developing neural lineage species. Int. J. Dev. Neurosci. 1995;13:213–240
  48. Mehler MF, Kessler JA. Hematolymphopoetic and inflammatory cytokines in neural development. Trends Neurosci. 1997;20:357–365
  49. Merrill JE. Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Dev. Neurosci. 1992;14:1–10
  50. Meyer TA, Wang JJ, Tiao GM, Ogle CK, Fischer JE, Hasselgren P. Sepsis and endotoxaemia in mice stimulate the expression of interleukin-1 and interleukin-6 in the central nervous system. Clin. Sci. 1997;92:519–525
  51. Mortensen PB, Pedersen CB, Westergaard T, Wohlfhart J, Ewald H, Mors O, et al. Effects of family history and place and season of birth on the risk of schizophrenia. New Engl. J. Med. 1999;340:603–608
  52. Nadeau S, Rivest S. Regulation of the gene encoding tumor necrosis factor alpha (TNF-α) in the rat brain and pituitary in response to different models of systemic immune challenge. J. Neuropathol. Exp. Neurol. 1999;58:61–77
  53. Nelson KB, Dambrosia JM, Grether JK, Phillips TM. Neonatal cytokines nad coagulation factor in children with cerebral palsy. Ann. Neurol. 1998;44:665–675
  54. Nguyen KT, Deak T, Owens SM, Kohno T, Fleshner M, Watkins LR, et al. Exposure to acute stress induces brain interleukin-1β protein in the rat. J. Neurosci. 1998;18:2239–2246
  55. O'Callaghan E, Sham PC, Takei N, Murray G, Glover G, Murray RM. The relationship of schizophrenic births to 16 infectious diseases. Br. J. Psychiatry. 1994;165:353–356
  56. Ornoy A, Altschuler G. Maternal endotoxemia, fetal anomalies, and central nervous system damage: a rat model of a human problem. Am. J. Obstet. Gynecol. 1976;124:196–204
  57. Pitossi F, del Rey A, Kabiersch A, Besedovsky H. Induction of cytokine transcripts in the central nervous system and pituitary following peripheral administration of endotoxin to mice. J. Neurosci. Res. 1997;48:287–298
  58. Quagliarello VJ, Wispelwey B, Long WJ, Scheld WM. Recombinant human interleukin-1 induces meningitis and blood–brain barrier injury in the rat. J. Clin. Invest. 1991;87:1360–1366
  59. Quan N, Stern EL, Whiteside MB, Herkenham M. Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. J. Neuroimmunol. 1999;93:72–80
  60. Salafia CM, Sherer DM, Spong CY, Lencki S, Eglinton GS, Parkash V, et al. Fetal but not maternal serum cytokine levels correlate with histologic acute placental infection. Am. J. Perinatol. 1997;14:419–422
  61. Sarnat HB. Role of the fetal ependyma. Ped. Neurol. 1992;8:163–178
  62. Sarnat HB. Ependymal reactions to injury, a review. J. Neuropathol. Exp. Neurol. 1995;54:1–15
  63. Steinborn A, von Gall C, Hildenbrand R, Stutte HJ, Kauffmann M. Indentification of placental cytokin producting cells in term and preterm labor. Obstet. Gynecol. 1998;91:329–335
  64. Torrey EF, Miller J, Rawlings R, Yolken RH. Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophr. Res. 1997;28:1–38
  65. Torrey EF, Rawlings R, Waldman IN. Schizophrenic births and viral diseases in two states. Schizophr. Res. 1988;1:73–77
  66. de Vries HE, Blom-Roosemalen MCM, van Oosten M, de Boer AG, van Berkel TJC, Breimer DD, et al. The influence of cytokines on the intergrity of the blood–brain barrier in vitro. J. Neuroimmunol. 1996;64:37–43
  67. Watson CG, Kucala T, Tilleskjor C, Jacobs L. Schizophrenic birth seasonality in relation to the incidence of infectious diseases and temperature extremes. Arch. Gen. Psychiatry. 1984;41:85–90
  68. Wenstrom KD, Andrews WW, Tamura T, DuBard MB, Johnston KE, Hemstreet GP. Elevated amniotic fluid interleukin-6 levels at genetic amniocentesis predict subsequent pregnancy loss. Am. J. Obstet. Gynecol. 1996;175:830–833
  69. Wispelwey B, Lesse AJ, Hansen EJ, Scheld WM. Haemophilus influenzae lipopolysaccharide-induced blood–brain-barrier permeability during experimental meningitis in the rat. J. Clin. Invest. 1988;82:1339–1346
  70. Yoon BH, Jun JK, Romero R, Park KL, Gomez R, Choi J, et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1β, and tumor necrosis factor-α), neonatal brain white matter lesions and cerebral palsy. Am. J. Obstet. Gynecol. 1997;177:19–26
  71. Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH, et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am. J. Obstet. Gynecol. 1995;172:960–970
  72. Yoon BH, Romero R, Kim CJ, Koo JN, Choe G, Syn HC, et al. High expression of tumor necrosis factor-α and interleukin-6 in periventricular leukomalacia. Am. J. Obstet. Gynecol. 1997;77:406–411
  73. Yoon BH, Romero R, Yang SH, Jun JK, Kim I, Choi J, et al. Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leuokmalacia. Am. J. Obstet. Gynecol. 1996;174:1433–1440

☆ Presented at the International Congress of Schizophrenia Research, Santa Fe, NM, 10 April 1999.

PII: S0920-9964(00)00032-3

Schizophrenia Research
Volume 47, Issue 1 , Pages 27-36 , 15 January 2001

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