Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1996 Jun;5(3):173–182. doi: 10.1155/S0962935196000233

The contribution of the immune system to parturition

R De Jongh 1,✉, Ph Jorens 2, I Student 3, R Heylen 1
PMCID: PMC2365787  PMID: 18475712

Abstract

The immune system plays a central role before and during parturition, including the main physiological processes of parturition: uterine contractions and cervical ripening. The immune system comprises white blood cells and their secretions. Polymorphonuclear cells and macrophages invade the cervical tissue and release compounds, such as oxygen radicals and enzymes, which break down the cervical matrix to allow softening and dilatation. During this inflammatory process, white blood cells undergo chemotaxis, adherence to endothelial cells, diapedesis, migration and activation. Factors that regulate white blood cell invasion and secretion include cytokines such as tumour necrosis factor and interleukins. Glucocorticoids, sex hormones and prostaglandins, affect cytokine synthesis. They also modulate the target cells, resulting in altered responses to cytokines. On the other hand, the immune system has profound effects on the hormonal system and prostaglandin synthesis. In animals, nitric oxide has marked effects on uterine quiescence during gestation. At the same time, it plays an important role in regulating the vascular tone of uterine arteries and has anti-adhesive effects on leukocytes. Cytokines are found in amniotic fluid, and in maternal and foetal serum at term and preterm. Several intrauterine cells have been shown to produce these cytoldnes. Since neither white blood cells, cytokines nor nitric oxide seem to be the ultimate intermediate for human parturition, the immune system is an additional but obligatory and underestimated component in the physiology of delivery. Scientists, obstetricians and anaesthesiologists must thus be aware of these processes.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Babior B. M. Oxidants from phagocytes: agents of defense and destruction. Blood. 1984 Nov;64(5):959–966. [PubMed] [Google Scholar]
  2. Bast A., Goris R. J. Oxidative stress. Biochemistry and human disease. Pharm Weekbl Sci. 1989 Dec 15;11(6):199–206. doi: 10.1007/BF01959411. [DOI] [PubMed] [Google Scholar]
  3. Boulanger C., Lüscher T. F. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest. 1990 Feb;85(2):587–590. doi: 10.1172/JCI114477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Camann W. R., Hortvet L. A., Hughes N., Bader A. M., Datta S. Maternal temperature regulation during extradural analgesia for labour. Br J Anaesth. 1991 Nov;67(5):565–568. doi: 10.1093/bja/67.5.565. [DOI] [PubMed] [Google Scholar]
  5. Casey M. L., Cox S. M., Word R. A., MacDonald P. C. Cytokines and infection-induced preterm labour. Reprod Fertil Dev. 1990;2(5):499–509. doi: 10.1071/rd9900499. [DOI] [PubMed] [Google Scholar]
  6. Cherouny P. H., Pankuch G. A., Romero R., Botti J. J., Kuhn D. C., Demers L. M., Appelbaum P. C. Neutrophil attractant/activating peptide-1/interleukin-8: association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants. Am J Obstet Gynecol. 1993 Nov;169(5):1299–1303. doi: 10.1016/0002-9378(93)90297-v. [DOI] [PubMed] [Google Scholar]
  7. Conrad K. P., Joffe G. M., Kruszyna H., Kruszyna R., Rochelle L. G., Smith R. P., Chavez J. E., Mosher M. D. Identification of increased nitric oxide biosynthesis during pregnancy in rats. FASEB J. 1993 Apr 1;7(6):566–571. [PubMed] [Google Scholar]
  8. Corcoran M. L., Stetler-Stevenson W. G., Brown P. D., Wahl L. M. Interleukin 4 inhibition of prostaglandin E2 synthesis blocks interstitial collagenase and 92-kDa type IV collagenase/gelatinase production by human monocytes. J Biol Chem. 1992 Jan 5;267(1):515–519. [PubMed] [Google Scholar]
  9. Craft J. B., Jr, Epstein B. S., Coakley C. S. Effect of lidocaine with epinephrine versus lidocaine (plain) on induced labor. Anesth Analg. 1972 Mar-Apr;51(2):243–246. [PubMed] [Google Scholar]
  10. Danforth D. N. The morphology of the human cervix. Clin Obstet Gynecol. 1983 Mar;26(1):7–13. doi: 10.1097/00003081-198303000-00005. [DOI] [PubMed] [Google Scholar]
  11. Dinchuk J. E., Car B. D., Focht R. J., Johnston J. J., Jaffee B. D., Covington M. B., Contel N. R., Eng V. M., Collins R. J., Czerniak P. M. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature. 1995 Nov 23;378(6555):406–409. doi: 10.1038/378406a0. [DOI] [PubMed] [Google Scholar]
  12. Dudley D. J., Trautman M. S., Mitchell M. D. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-decidual interface. J Clin Endocrinol Metab. 1993 Feb;76(2):404–410. doi: 10.1210/jcem.76.2.8432783. [DOI] [PubMed] [Google Scholar]
  13. Fuchs A. R., Fuchs F., Husslein P., Soloff M. S., Fernström M. J. Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor. Science. 1982 Mar 12;215(4538):1396–1398. doi: 10.1126/science.6278592. [DOI] [PubMed] [Google Scholar]
  14. Fuchs A. R., Husslein P., Fuchs F. Oxytocin and the initiation of human parturition. II. Stimulation of prostaglandin production in human decidua by oxytocin. Am J Obstet Gynecol. 1981 Nov 15;141(6):694–697. doi: 10.1016/s0002-9378(15)33313-5. [DOI] [PubMed] [Google Scholar]
  15. Fukuoka M., Yasuda K., Fujiwara H., Kanzaki H., Mori T. Interactions between interferon gamma, tumour necrosis factor alpha, and interleukin-1 in modulating progesterone and oestradiol production by human luteinized granulosa cells in culture. Hum Reprod. 1992 Nov;7(10):1361–1364. doi: 10.1093/oxfordjournals.humrep.a137574. [DOI] [PubMed] [Google Scholar]
  16. Gardner H. W. Oxygen radical chemistry of polyunsaturated fatty acids. Free Radic Biol Med. 1989;7(1):65–86. doi: 10.1016/0891-5849(89)90102-0. [DOI] [PubMed] [Google Scholar]
  17. Goodwin T. M., Paul R., Silver H., Spellacy W., Parsons M., Chez R., Hayashi R., Valenzuela G., Creasy G. W., Merriman R. The effect of the oxytocin antagonist atosiban on preterm uterine activity in the human. Am J Obstet Gynecol. 1994 Feb;170(2):474–478. doi: 10.1016/s0002-9378(94)70214-4. [DOI] [PubMed] [Google Scholar]
  18. Granger D. N., Kubes P. The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol. 1994 May;55(5):662–675. [PubMed] [Google Scholar]
  19. Gunja-Smith Z., Woessner J. F., Jr Content of the collagen and elastin cross-links pyridinoline and the desmosines in the human uterus in various reproductive states. Am J Obstet Gynecol. 1985 Sep 1;153(1):92–95. doi: 10.1016/0002-9378(85)90602-7. [DOI] [PubMed] [Google Scholar]
  20. Helset E., Sildnes T., Seljelid R., Konopski Z. S. Endothelin-1 stimulates human monocytes in vitro to release TNF-alpha , IL-1beta and IL-6. Mediators Inflamm. 1993;2(6):417–422. doi: 10.1155/S0962935193000596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hiro D., Ito A., Matsuta K., Mori Y. Hyaluronic acid is an endogenous inducer of interleukin-1 production by human monocytes and rabbit macrophages. Biochem Biophys Res Commun. 1986 Oct 30;140(2):715–722. doi: 10.1016/0006-291x(86)90790-4. [DOI] [PubMed] [Google Scholar]
  22. Hla T., Ristimäki A., Appleby S., Barriocanal J. G. Cyclooxygenase gene expression in inflammation and angiogenesis. Ann N Y Acad Sci. 1993 Nov 30;696:197–204. doi: 10.1111/j.1749-6632.1993.tb17152.x. [DOI] [PubMed] [Google Scholar]
  23. Imlay J. A., Linn S. DNA damage and oxygen radical toxicity. Science. 1988 Jun 3;240(4857):1302–1309. doi: 10.1126/science.3287616. [DOI] [PubMed] [Google Scholar]
  24. Imura H., Fukata J., Mori T. Cytokines and endocrine function: an interaction between the immune and neuroendocrine systems. Clin Endocrinol (Oxf) 1991 Aug;35(2):107–115. doi: 10.1111/j.1365-2265.1991.tb03506.x. [DOI] [PubMed] [Google Scholar]
  25. Ito A., Hiro D., Ojima Y., Mori Y. Spontaneous production of interleukin-1-like factors from pregnant rabbit uterine cervix. Am J Obstet Gynecol. 1988 Jul;159(1):261–265. doi: 10.1016/0002-9378(88)90532-7. [DOI] [PubMed] [Google Scholar]
  26. Jacobs A. L., Carson D. D. Uterine epithelial cell secretion of interleukin-1 alpha induces prostaglandin E2 (PGE2) and PGF2 alpha secretion by uterine stromal cells in vitro. Endocrinology. 1993 Jan;132(1):300–308. doi: 10.1210/endo.132.1.8419129. [DOI] [PubMed] [Google Scholar]
  27. Johnson K. J., Varani J., Smolen J. E. Neutrophil activation and function in health and disease. Immunol Ser. 1992;57:1–46. [PubMed] [Google Scholar]
  28. Jorens P. G., Matthys K. E., Bult H. Modulation of nitric oxide synthase activity in macrophages. Mediators Inflamm. 1995;4(2):75–89. doi: 10.1155/S0962935195000135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kelly R. W., Leask R., Calder A. A. Choriodecidual production of interleukin-8 and mechanism of parturition. Lancet. 1992 Mar 28;339(8796):776–777. doi: 10.1016/0140-6736(92)91896-g. [DOI] [PubMed] [Google Scholar]
  30. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kunkel S. L., Standiford T., Kasahara K., Strieter R. M. Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res. 1991 Jan-Feb;17(1):17–23. doi: 10.3109/01902149109063278. [DOI] [PubMed] [Google Scholar]
  32. Laham N., Rice G. E., Bishop G. J., Hansen M. B., Bendtzen K., Brennecke S. P. Elevated plasma interleukin 6: a biochemical marker of human preterm labour. Gynecol Obstet Invest. 1993;36(3):145–147. doi: 10.1159/000292614. [DOI] [PubMed] [Google Scholar]
  33. Lees C., Campbell S., Jauniaux E., Brown R., Ramsay B., Gibb D., Moncada S., Martin J. F. Arrest of preterm labour and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor. Lancet. 1994 May 28;343(8909):1325–1326. doi: 10.1016/s0140-6736(94)92468-6. [DOI] [PubMed] [Google Scholar]
  34. Lewis M. S., Whatley R. E., Cain P., McIntyre T. M., Prescott S. M., Zimmerman G. A. Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. J Clin Invest. 1988 Dec;82(6):2045–2055. doi: 10.1172/JCI113825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lundin-Schiller S., Mitchell M. D. Prostaglandin production by human chorion laeve cells in response to inflammatory mediators. Placenta. 1991 Jul-Aug;12(4):353–363. doi: 10.1016/0143-4004(91)90343-e. [DOI] [PubMed] [Google Scholar]
  36. López Bernal A., Watson S. P., Phaneuf S., Europe-Finner G. N. Biochemistry and physiology of preterm labour and delivery. Baillieres Clin Obstet Gynaecol. 1993 Sep;7(3):523–552. doi: 10.1016/s0950-3552(05)80447-x. [DOI] [PubMed] [Google Scholar]
  37. McCord J. M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985 Jan 17;312(3):159–163. doi: 10.1056/NEJM198501173120305. [DOI] [PubMed] [Google Scholar]
  38. Mela-Riker L., Tavakoli H. Mitochondrial function in shock. Am J Emerg Med. 1984 Jan;2(1):2–7. doi: 10.1016/0735-6757(84)90103-7. [DOI] [PubMed] [Google Scholar]
  39. Miele L., Cordella-Miele E., Mantile G., Peri A., Mukherjee A. B. Uteroglobin and uteroglobin-like proteins: the uteroglobin family of proteins. J Endocrinol Invest. 1994 Sep;17(8):679–692. doi: 10.1007/BF03349687. [DOI] [PubMed] [Google Scholar]
  40. Mitchell M. D., Edwin S., Romero R. J. Prostaglandin biosynthesis by human decidual cells: effects of inflammatory mediators. Prostaglandins Leukot Essent Fatty Acids. 1990 Sep;41(1):35–38. doi: 10.1016/0952-3278(90)90128-8. [DOI] [PubMed] [Google Scholar]
  41. Mitchell M. D., Trautman M. S., Dudley D. J. Immunoendocrinology of preterm labour and delivery. Baillieres Clin Obstet Gynaecol. 1993 Sep;7(3):553–575. doi: 10.1016/s0950-3552(05)80448-1. [DOI] [PubMed] [Google Scholar]
  42. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  43. Morel F., Doussiere J., Vignais P. V. The superoxide-generating oxidase of phagocytic cells. Physiological, molecular and pathological aspects. Eur J Biochem. 1991 Nov 1;201(3):523–546. doi: 10.1111/j.1432-1033.1991.tb16312.x. [DOI] [PubMed] [Google Scholar]
  44. Naito Y., Fukata J., Shindo K., Ebisui O., Murakami N., Tominaga T., Nakai Y., Mori K., Kasting N. W., Imura H. Effects of interleukins on plasma arginine vasopressin and oxytocin levels in conscious, freely moving rats. Biochem Biophys Res Commun. 1991 Feb 14;174(3):1189–1195. doi: 10.1016/0006-291x(91)91547-p. [DOI] [PubMed] [Google Scholar]
  45. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  46. Noble P. W., Lake F. R., Henson P. M., Riches D. W. Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages. J Clin Invest. 1993 Jun;91(6):2368–2377. doi: 10.1172/JCI116469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Osmers R., Rath W., Pflanz M. A., Kuhn W., Stuhlsatz H. W., Szeverényi M. Glycosaminoglycans in cervical connective tissue during pregnancy and parturition. Obstet Gynecol. 1993 Jan;81(1):88–92. [PubMed] [Google Scholar]
  48. Pober J. S., Cotran R. S. The role of endothelial cells in inflammation. Transplantation. 1990 Oct;50(4):537–544. doi: 10.1097/00007890-199010000-00001. [DOI] [PubMed] [Google Scholar]
  49. Rivier C., Vale W. In the rat, interleukin-1 alpha acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. Endocrinology. 1989 May;124(5):2105–2109. doi: 10.1210/endo-124-5-2105. [DOI] [PubMed] [Google Scholar]
  50. Romero R., Brody D. T., Oyarzun E., Mazor M., Wu Y. K., Hobbins J. C., Durum S. K. Infection and labor. III. Interleukin-1: a signal for the onset of parturition. Am J Obstet Gynecol. 1989 May;160(5 Pt 1):1117–1123. doi: 10.1016/0002-9378(89)90172-5. [DOI] [PubMed] [Google Scholar]
  51. Saito S., Kasahara T., Kato Y., Ishihara Y., Ichijo M. Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition. Cytokine. 1993 Jan;5(1):81–88. doi: 10.1016/1043-4666(93)90027-3. [DOI] [PubMed] [Google Scholar]
  52. Sanderud J., Bjøro K., Saugstad O. D. Oxygen radicals stimulate thromboxane and prostacyclin synthesis and induce vasoconstriction in pig lungs. Scand J Clin Lab Invest. 1993 Aug;53(5):447–455. doi: 10.1080/00365519309092539. [DOI] [PubMed] [Google Scholar]
  53. Sapolsky R., Rivier C., Yamamoto G., Plotsky P., Vale W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 1987 Oct 23;238(4826):522–524. doi: 10.1126/science.2821621. [DOI] [PubMed] [Google Scholar]
  54. Sibille Y., Merrill W. W., Naegel G. P., Care S. B., Cooper J. A., Jr, Reynolds H. Y. Human alveolar macrophages release a factor that inhibits phagocyte function. Am J Respir Cell Mol Biol. 1989 Nov;1(5):407–416. doi: 10.1165/ajrcmb/1.5.407. [DOI] [PubMed] [Google Scholar]
  55. Siiteri P. K., Febres F., Clemens L. E., Chang R. J., Gondos B., Stites D. Progesterone and maintenance of pregnancy: is progesterone nature's immunosuppressant? Ann N Y Acad Sci. 1977 Mar 11;286:384–397. doi: 10.1111/j.1749-6632.1977.tb29431.x. [DOI] [PubMed] [Google Scholar]
  56. Smith W. L. Prostanoid biosynthesis and mechanisms of action. Am J Physiol. 1992 Aug;263(2 Pt 2):F181–F191. doi: 10.1152/ajprenal.1992.263.2.F181. [DOI] [PubMed] [Google Scholar]
  57. Suzuki Y., Yamaguchi T. Effects of hyaluronic acid on macrophage phagocytosis and active oxygen release. Agents Actions. 1993 Jan;38(1-2):32–37. doi: 10.1007/BF02027210. [DOI] [PubMed] [Google Scholar]
  58. Thorat S. P., Thatte U. M., Pai N., Dahanukar S. A. Effect of prolactin on neutrophils and monocytes. Acta Haematol. 1993;89(4):219–220. doi: 10.1159/000204572. [DOI] [PubMed] [Google Scholar]
  59. Tominaga T., Fukata J., Naito Y., Usui T., Murakami N., Fukushima M., Nakai Y., Hirai Y., Imura H. Prostaglandin-dependent in vitro stimulation of adrenocortical steroidogenesis by interleukins. Endocrinology. 1991 Jan;128(1):526–531. doi: 10.1210/endo-128-1-526. [DOI] [PubMed] [Google Scholar]
  60. Trautman M. S., Dudley D. J., Edwin S. S., Collmer D., Mitchell M. D. Amnion cell biosynthesis of interleukin-8: regulation by inflammatory cytokines. J Cell Physiol. 1992 Oct;153(1):38–43. doi: 10.1002/jcp.1041530107. [DOI] [PubMed] [Google Scholar]
  61. VASICKA A., KRETCHMER H. Effect of conduction and inhalation anesthesia on uterine contractions. Experimental study of the influence of anesthesia on intra-amniotic pressures. Am J Obstet Gynecol. 1961 Sep;82:600–611. doi: 10.1016/0002-9378(61)90278-2. [DOI] [PubMed] [Google Scholar]
  62. Vince G. S., Starkey P. M., Jackson M. C., Sargent I. L., Redman C. W. Flow cytometric characterisation of cell populations in human pregnancy decidua and isolation of decidual macrophages. J Immunol Methods. 1990 Sep 14;132(2):181–189. doi: 10.1016/0022-1759(90)90028-t. [DOI] [PubMed] [Google Scholar]
  63. Wardlaw A. Leucocyte adhesion to endothelium. Clin Exp Allergy. 1990 Nov;20(6):619–626. doi: 10.1111/j.1365-2222.1990.tb02700.x. [DOI] [PubMed] [Google Scholar]
  64. Yallampalli C., Garfield R. E., Byam-Smith M. Nitric oxide inhibits uterine contractility during pregnancy but not during delivery. Endocrinology. 1993 Oct;133(4):1899–1902. doi: 10.1210/endo.133.4.8404632. [DOI] [PubMed] [Google Scholar]
  65. van Furth R., Cohn Z. A., Hirsch J. G., Humphrey J. H., Spector W. G., Langevoort H. L. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull World Health Organ. 1972;46(6):845–852. [PMC free article] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES