Amniotic fluid interleukin-6 and preterm delivery: a review

doi:10.1016/S0029-7844(00)00875-9

Obstetrics & Gynecology

Volume 95, Issue 6, Part 2, June 2000, Pages 1056-1064

https://doi.org/10.1016/S0029-7844(00)00875-9 Get rights and content

Abstract

Objective: To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection.

Data Sources: We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords “labor/infant,” “premature,” “cytokines/interleukin-6,” and “AF.” We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles.

Methods of Study Selection: The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery.

Tabulation, Integration, and Results: There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33–70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered.

Conclusion: Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.

Section snippets

Data sources

For the main exposure (AF IL-6) and outcome (preterm labor or preterm delivery) of interest in this review article, we searched the English-language human literature in MEDLINE (1966 through September 1999), using the keywords “labor or infant,” “premature,” and “cytokines or interleukin-6,” and “amniotic fluid.” We also examined abstracts from the 19th Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, California, 1999 and from the 32nd Annual Meeting of the Society for

Tabulation, integration, and results

Table 1 and Table 2 summarize results from studies that examined the association between AF IL-6 in intra-amniotic infection and preterm labor or preterm delivery and that we could fit into the paradigm presented.39, 41, 43, 46, 53, 54, 55, 56, 57, 58, 59, 60, 61 Other studies are referred to in the text when appropriate. Because of the importance of appropriate specimen collection and storage in laboratory studies of AF, we summarized this information in Table 1. Storage and collection are

Conclusion

We conclude that the literature has reached consensus that elevated AF IL-6 is consistently associated with intra-amniotic infection and preterm delivery. Future research should focus on clinical application of ELISA assays to detect AF IL-6 as it might indicate intra-amniotic infection. It should be noted that finding elevated AF IL-6 does not identify the specific organisms involved in intra-amniotic infection. Identification remains an important scientific as well as clinical goal.

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Citation Excerpt :
Accordingly, we propose that an increase of IL-10 levels in AF induced by EE could acts as protective factor against a potential inflammatory state. On the other hand, IL-6 has been shown to be essential in the triggering of term and preterm labor in mice and in humans (El-bastawissi et al., 2000; Robertson et al., 2010). We observed increased IL-6 levels in the AF in both groups (CE and EE) in response to LPS.
The production of pro-inflammatory cytokines during inflammatory processes has been associated with preterm birth (PTB) and fetal injury in humans and mice. We previously demonstrated that exposition to an enriched environment (EE), defined as a noninvasive and biological significant stimulus of the sensory pathway combined with voluntary physical activity, prevented PTB and perinatal death induced by the systemic administration of bacterial lipopolysaccharide (LPS) in mice. This work aimed to analyze whether EE modulates the immune response to the inflammatory process induced by LPS in peripheral blood and the amniotic fluid (AF). We observed that EE modulated maternal white blood cell count and its response to LPS. Furthermore, we found higher levels of IL-10 and a higher percentage of B cells in AF from EE exposed mothers compared to controls. Albeit LPS significantly increased IL-6 levels in AF from both groups, it was 3.6 times higher in control environment (CE) exposed group when compared to EE. Similarly, levels of IL-22 were significantly increased by LPS in both groups, but it was 6.7 times higher in EE group. Interestingly, levels of PGE2 in AF were only increased in the EE-LPS treated group, and a positive correlation between IL-22 and PGE2 levels was observed. During lactation, EE prevented LPS-induced delay in physical landmarks analyzed to assess offspring development. Our results suggest that EE modulates the immune response to systemic LPS-administration protecting the offspring. We propose that an EE-like protocol could be designed for pregnant women aiming at preventing the sequelae present in premature children.
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^☆: This work was supported by grant R40 MC 00113 from the Maternal and Child Health Bureau (Title V, Social Security Act), Health Resources and Services Administration, Department of Health and Human Services.

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ReviewsAmniotic fluid interleukin-6 and preterm delivery: a review☆

Abstract

Section snippets

Data sources

Tabulation, integration, and results

Conclusion

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Eur J Pharmacol

Am J Obstet Gynecol

Cytokine

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Biochem Biophys Res Commun

Biochem Biophys Res Commun

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Cytokine

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Lancet

Reviews
Amniotic fluid interleukin-6 and preterm delivery: a review☆