Journal Mobile Options
Table of Contents
Vol. 89, No. 3, 2006
Issue release date: April 2006
Biol Neonate 2006;89:183–189
(DOI:10.1159/000089180)

Elevation of Cytokine Concentrations in Asphyxiated Neonates

Okazaki K. · Nishida A. · Kato M. · Kozawa K. · Uga N. · Kimura H.
aTokyo Metropolitan Hachioji Children’s Hospital, Hachioji, and bTokyo Metropolitan Kiyose Children’s Hospital, Kiyose, Tokyo, cGunma Prefectural Institute of Public Health and Environmental Sciences, Maebashi, Gunma, and dDivision of Neonatology, Perinatal Center, Toho University School of Medicine, Ota-ku, Tokyo, Japan

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background: Various cytokines are reportedly associated with many neonatal diseases. Asphyxia is considered to result in ischemia-reperfusion injuries and induces abnormal inflammatory responses involving excessive cytokine production. Objectives: To evaluate alteration in sera levels of various cytokines/chemokines in case of perinatal asphyxia at birth. Methods: In orderto determine the concentrations of various cytokines/chemokines in sera, we used a highly sensitive fluorescence microsphere method. We measured the concentration of 8 types of cytokines/chemokines in sera obtained from 17 cases of asphyxia, 10 normal neonates, and 6 healthy adults. Results: The concentrations of IL-6, IL-8, and IL-10 in the sera of asphyxiated neonates were higher than those in the normal neonates. Irrespective of the presence or absence of asphyxia, sera concentrations of IL-2, IL-4, IFN-γ, and TNF-α were higher in the neonates than those in the adults. The concentration of IFN-γ in the asphyxiated neonates was lower than that in the normal neonates. Sera levels of IL-10 were higher in the asphyxiated cases than those in the normal neonates. The sera levels of IL-6, IL-8, and IL-10 in asphyxiated neonates with either a poor outcome or death were higher than those without poor outcomes. Conclusions: The concentrations of various types of cytokines/chemokines were different in neonatal sera and some of them increased drastically during asphyxia. The concentration of an anti-inflammatory cytokine IL-10 was elevated in asphyxiated neonates immediately after birth, thereby suggesting that IL-10 might be associated with neuroprotective functions.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Volpe JJ: Hypoxic-ischemic encephalopathy; in Volpe JJ (eds): Neurology of the Newborn, ed 4. Philadelphia, Saunders, 2001, pp 217–394.
  2. Hallenbeck JM, Dutka AJ, Tanishima T, Kochanek PM, Kumaroo KK, Thompson CB, Obrenovitch TP, Contreras TJ: Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke 1986;17:246–253.
  3. Hammerman C, Kaplan M: Ischemia and reperfusion injury: the ultimate pathophysiologic paradox. Clin Perinatol 1998;25:757–777.
  4. Kondo M, Itoh S, Isobe K, Kondo M, Kunikata T, Imai T, Onishi S: Chemiluminescence because of the production of reactive oxygen species in the lungs of newborn piglets during resuscitation periods after asphyxia load. Pediatr Res 2000;47:524–527.
  5. Bona E, Andersson AL, Blomgren K, Gilland E, Puka-Sundvall M, Gustafson K, Hagberg H: Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. Pediatr Res 1999;45:500–509.
  6. Oppenheim JJ: Cytokines: past, present, and future. Int J Hematol 2001;74:3–8.
  7. Baumann H, Gauldie J: The acute phase response. Immunol Today 1994;15:74–80.
  8. Hodge G, Hodge S, Haslam R, McPhee A, Sepulveda H, Morgan E, Nicholson I, Zola H: Rapid simultaneous measurement of multiple cytokines using 100 microl sample volumes: association with neonatal sepsis. Clin Exp Immunol 2004;137:402–407.
  9. Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM: Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics 2002;110:673–680.
  10. Toledo-Pereyra LH, Lopez-Neblina F, Toledo AH: Reactive oxygen species and molecular biology of ischemia/reperfusion. Ann Transplant 2004;9:81–83.
  11. Seino Y, Ikeda U, Minezaki KK, Funayama H, Kasahara T, Konishi K, Shimada K: Expression of cytokine-induced neutrophil chemoattractant in rat cardiac myocytes. J Mol Cell Cardiol 1995;27:2043–2051.
  12. Fellman V, Raivio KO: Reperfusion injury as the mechanism of brain damage after perinatal asphyxia. Pediatr Res 1997;41:599–606.
  13. 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.
  14. Romero R, Maymon E, Pacora P, Gomez R, Mazor M, Yoon BH, Berry SM: Further observations on the fetal inflammatory response syndrome: a potential homeostatic role for the soluble receptors of tumor necrosis factor alpha. Am J Obstet Gynecol 2000;183:1070–1077.
  15. Jokic M, Guillois B, Cauquelin B, Giroux JD, Bessis JL, Morello R, Levy G, Ballet JJ: Fetal distress increases interleukin-6 and interleukin-8 and decreases tumour necrosis factor-alpha cord blood levels in noninfected full-term neonates. BJOG 2000;107:420–425.
  16. Silveira RC, Procianoy RS: Interleukin-6 and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy. J Pediatr 2003;143:625–629.
  17. Xanthou M, Fotopoulos S, Mouchtouri A, Lipsou N, Zika I, Sarafidou J: Inflammatory mediators in perinatal asphyxia and infection. Acta Paediatr Suppl 2002;91:92–97.
  18. Fotopoulos S, Pavlou K, Skouteli H, Papassotiriou I, Lipsou N, Xanthou M: Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection. Biol Neonate 2001;79:213–218.
  19. Savman K, Blennow M, Gustafson K, Tarkowski E, Hagberg H: Cytokine response in cerebrospinal fluid after birth asphyxia. Pediatr Res 1998;43:746–751.
  20. Phelan JP, Martin GI, Korst LM: Birth asphyxia and cerebral palsy. Clin Perinatol 2005;32:61–76.
  21. Buonocore G, De Filippo M, Gioia D, Picciolini E, Luzzi E, Bocci V, Bracci R: Maternal and neonatal plasma cytokine levels in relation to mode of delivery. Biol Neonate 1995;68:104–110.
  22. Kimura H, Kato M, Ikeda M, Nagai A, Okada Y, Naito S, Oshima S, Taniguchi K, Kozawa K, Morikawa A: Sulfonated human immunoglobulin enhances CD16-linked CD11b expression on human neutrophils. Cell Biol Int 2003;27:913–919.
  23. Chiesa C, Pellegrini G, Panero A, De Luca T, Assumma M, Signore F, Pacifico L: Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia. Eur J Clin Invest 2003;33:352–358.
  24. Yoon BH, Jun JK, Romero R, Park KH, Gomez R, Choi JH, Kim IO: Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1997;177:19–26.
  25. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP: The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 1995;273:117–123.
  26. Hashimoto M, Nishida A, Minakami H, Takashima Y, Kato M, Okada Y, Ogawa Y, Itoh S, Kimura H: Decreased expression of L-selectin on peripheral blood polymorphonuclear leukocytes in neonates with severe asphyxia. Biol Neonate 2002;81:95–98.
  27. Hata T, Kawamura T, Inada K, Fujiwaki R, Ariyuki Y, Hata K, Kitao M: Interleukin-6, interleukin-8, and granulocyte elastase in newborns with fetal distress. Gynecol Obstet Invest 1996;42:174–177.
  28. Hagberg H, Gilland E, Bona E, Hanson LA, Hahin-Zoric M, Blennow M, Holst M, McRae A, Soder O: Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats. Pediatr Res 1996;40:603–609.
  29. Foster-Barber A, Dickens B, Ferriero DM: Human perinatal asphyxia: correlation of neonatal cytokines with MRI and outcome. Dev Neurosci 2001;23:213–218.
  30. Bell MJ, Kochanek PM, Doughty LA, Carcillo JA, Adelson PD, Clark RS, Wisniewski SR, Whalen MJ, DeKosky ST: Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children. J Neurotrauma 1997;14:451–457.
  31. Froen JF, Munkeby BH, Stray-Pedersen B, Saugstad OD: Interleukin-10 reverses acute detrimental effects of endotoxin-induced inflammation on perinatal cerebral hypoxia-ischemia. Brain Res 2002;28;942:87–94.
  32. Herrero C, Hu X, Li WP, Samuels S, Sharif MN, Kotenko S, Ivashkiv LB: Reprogramming of IL-10 activity and signaling by IFN-gamma. J Immunol 2003;171:5034–5041.
  33. Liu XS, Xu Y, Hardy L, Khammanivong V, Zhao W, Fernando GJ, Leggatt GR, Frazer IH: IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral epitope in a primed host. J Immunol 2003;171:4765–4772.
  34. Protonotariou E, Malamitsi-Puchner A, Giannaki G, Rizos D, Phocas I, Sarandakou A: Patterns of inflammatory cytokine serum concentrations during the perinatal period. Early Hum Dev 1999;56:31–38.
  35. Protonotariou E, Malamitsi-Puchner A, Rizos D, Sarandakou A, Makrakis E, Salamolekis E: Alterations in Thl/Th2 cytokine concentrations in early neonatal life. J Matern Fetal Neonatal Med 2003;14:407–410.
  36. Protonotariou E, Malamitsi-Puchner A, Rizos D, Papagianni B, Moira E, Sarandakou A, Botsis D: Age-related differentiations of Th1/Th2 cytokines in newborn infants. Mediators Inflamm 2004;13:89–92.
  37. Sarandakou A, Giannaki G, Malamitsi-Puchner A, Rizos D, Hourdaki E, Protonotariou E, Phocas I: Inflammatory cytokines in newborn infants. Mediators Inflamm 1998;7:309–312.
  38. Saito S, Sakai M, Sasaki Y, Tanebe K, Tsuda H, Michimata T: Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1:Th2 cell ratio during normal human pregnancy and preeclampsia. Clin Exp Immunol 1999;117:550–555.
  39. Asakura H, Ichikawa H, Nakabayashi M, Ando K, Kaneko K, Kawabata M, Tani A, Satoh M, Takahashi K, Sakamoto S: Perinatal risk factors related to neurologic outcomes of term newborns with asphyxia at birth: a prospective study. J Obstet Gynaecol Res 2000;26:313–324.
  40. Van Den Anker JN, Van Der Heijden BJ, Hop WC, Schoemaker RC, Broerse HM, Neijens HJ, De Groot R: The effect of asphyxia on the pharmacokinetics of ceftazidime in the term newborn. Pediatr Res 1995;38:808–811.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50