Transfer of Proinflammatory Cytokines Across Term Placenta

OBJECTIVE: Increased concentrations of proinflammatory cytokines in amniotic fluid indicate the presence of intra-amniotic inflammation and increase the risk of preterm birth, cerebral palsy, and bronchopulmonary dysplasia. The purpose of this study was to find out if the proinflammatory cytokines, tumor necrosis factor alpha (TNF-&agr;), interleukin (IL)-1&bgr;, and IL-6, transfer across the placenta, and thereby determine whether intra-amniotic inflammatory response, measured from the amniotic fluid, is of maternal or fetal origin. METHODS: Nineteen placentas from healthy women undergoing elective cesarean delivery at term with intact membranes and without labor, were dually perfused ex vivo in an open circulation system for either 30 minutes or 2 hours. Tumor necrosis factor-&agr;, IL-1&bgr;, and IL-6 were added to maternal or fetal circulation in a concentration usually found in chorioamnionitis. As a reference, placentas without added cytokine were also perfused. The concentrations of cytokines were determined by enzyme immunoassays (enzyme-linked immunosorbent assay [ELISA]). RESULTS: After the addition of the cytokine to the arterial perfusate, the venous concentration on the same side of the placenta increased rapidly and reached a plateau at 10 minutes. No transfer of any cytokine in either direction was detected. Some endogenous release of IL-6 was observed in response to the perfusion. CONCLUSION: Proinflammatory cytokines do not cross normal term placenta. LEVEL OF EVIDENCE: II-1

[1]  Roberto Romero,et al.  The fetal inflammatory response syndrome. , 1998, American journal of obstetrics and gynecology.

[2]  W. Byrd,et al.  Transfer of Inflammatory Cytokines Across the Placenta , 2004, Obstetrics and gynecology.

[3]  Monica Lahra,et al.  A fetal response to chorioamnionitis is associated with early survival after preterm birth. , 2004, American journal of obstetrics and gynecology.

[4]  Z. Zaki,et al.  Maternal serum interleukin‐6, interleukin‐8, tumor necrosis factor‐α and interferon‐γ in preterm labor , 2003 .

[5]  T. Chaiworapongsa,et al.  Intrauterine infection and the development of cerebral palsy , 2003, BJOG : an international journal of obstetrics and gynaecology.

[6]  M. Mitchell,et al.  Critical Paracrine Interactions Between TNF-α and IL-10 Regulate Lipopolysaccharide-Stimulated Human Choriodecidual Cytokine and Prostaglandin E2 Production1 , 2003, The Journal of Immunology.

[7]  Z. Zaki,et al.  Maternal serum interleukin-6, interleukin-8, tumor necrosis factor-alpha and interferon-gamma in preterm labor. , 2003, Acta obstetricia et gynecologica Scandinavica.

[8]  M. Shaarawy,et al.  Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection , 2002, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[9]  L. Vatten,et al.  Histologic chorioamnionitis and umbilical serum levels of pro‐inflammatory cytokines and cytokine inhibitors , 2002, BJOG : an international journal of obstetrics and gynaecology.

[10]  B. Calhoun,et al.  The effects of hypoxia and hyperoxia on fetal-placental vascular tone and inflammatory cytokine production. , 2001, American journal of obstetrics and gynecology.

[11]  M. Türe,et al.  Maternal serum tumor necrosis factor-alpha in patients with preterm labor. , 2001, The Journal of reproductive medicine.

[12]  A. Lyon.  Chronic lung disease of prematurity. The role of intra-uterine infection , 2000, European Journal of Pediatrics.

[13]  B. Calhoun,et al.  Hypoperfusion causes increased production of interleukin 6 and tumor necrosis factor alpha in the isolated, dually perfused placental cotyledon. , 2000, American journal of obstetrics and gynecology.

[14]  S. Loibl,et al.  Predictive value of serum interleukin‐6 and ‐8 levels in preterm labor or rupture of the membranes , 2000, Acta obstetricia et gynecologica Scandinavica.

[15]  J. Hauth,et al.  Intrauterine infection and preterm delivery. , 2000, The New England journal of medicine.

[16]  A. Leviton,et al.  Role of the fetus in perinatal infection and neonatal brain damage , 2000, Current opinion in pediatrics.

[17]  F. Denison,et al.  Cytokine secretion by human fetal membranes, decidua and placenta at term. , 1998, Human reproduction.

[18]  F. Ghezzi,et al.  A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. , 1998, American journal of obstetrics and gynecology.

[19]  A. Rubinstein,et al.  Receptor-Mediated Maternofetal Transfer of ImmunoglobulinsInhibition of Transport of Anti-HIV-1 Immunoglobulin by Generic Immunoglobulins in the in vitro Perfused Placenta , 1998, International Archives of Allergy and Immunology.

[20]  C. Spong,et al.  Fetal but not maternal serum cytokine levels correlate with histologic acute placental inflammation. , 1997, American journal of perinatology.

[21]  H. Kiss,et al.  The Transfer of Interleukin‐8 Across the Human Placenta Perfused In Vitro , 1996, Obstetrics and gynecology.

[22]  C. Sibley,et al.  Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy. , 1995, The Journal of clinical investigation.

[23]  J. Dancis,et al.  Transfer across the perfused human placenta of antipyrine, sodium and leucine. , 1972, American journal of obstetrics and gynecology.