Abstract
Purpose: Cervical dilatation during parturition is associated with a significant increase of interleukin (IL)-6 and IL-8. The purpose of this study was to localize the respective messenger RNA and to quantitate their protein levels during various stages of dilatation.
Methods: Protein extracts from 34 biopsy specimens of the lower uterine segment at various stages of cervical dilatation (<2, 2 to <4, 4–6, and >6 cm) were subjected to enzyme linked immunosorbent assay for IL-6 and IL-8 to document their concentration. The respective mRNA expression was studied using reverse transcriptase PCR using IL-6 and IL-8 specific primers. Localization of IL-6 and IL-8 was done by in situ hybridization using biotinylated probes.
Results: The IL-6 and IL-8 concentrations increased significantly in the lower uterine segment tissues at 4–6 cm of dilatation. Expression of IL-8 was seen in all the tissues at or more than 4 cm dilatation, whereas IL-6 expression was inconsistent. In situ hybridization localized IL-6 and IL-8 mRNA to the glandular epithelium.
Conclusions: The increase in the inflammatory cytokines (IL-6 and IL-8) during parturition is associated with cervical effacement.
Keywords: Cervix, cytokines, IL-6, IL-8, messenger RNA, parturition
Full Text
The Full Text of this article is available as a PDF (215.4 KB).
REFERENCES
- 1.Osmers R, Rath W, Adelmann-Grill BC, Fittkow C, Kuloczik M, Szeverenyi M, Tschesche H, Kuhn W. Origin of cervical collagenase during parturition. Am J Obstet Gynecol. 1992;166:1455–1460. doi: 10.1016/0002-9378(92)91619-l. [DOI] [PubMed] [Google Scholar]
- 2.Barclay CG, Brennand JE, Kelly RW, Calder AA. Interleukin-8 production by the human cervix. Am J Obstet Gynecol. 1993;169:625–632. doi: 10.1016/0002-9378(93)90634-u. [DOI] [PubMed] [Google Scholar]
- 3.Winkler M, Fischer DC, Hlubek M, Leur E, Haubeck HD, Rath W. Interleukin-1beta and Interleukin-8 concentrations in the lower uterine segment during parturition at term. Obstet Gynecol. 1998;91:945–949. doi: 10.1016/s0029-7844(98)00098-2. [DOI] [PubMed] [Google Scholar]
- 4.Chwalisz K, Benson M, Scholz P, Daum J, Beier HM, Hegele-Hartung C. Cervical ripening with the cytokines interleukin 8, interleukin 1ß and tumor necrosis factor α in guinea pigs. Hum Reprod. 1994;9:2173–2181. doi: 10.1093/oxfordjournals.humrep.a138413. [DOI] [PubMed] [Google Scholar]
- 5.Romero R, Avila C, Santhanam U, Sehgal PB. Amniotic fluid interleukin 6 in preterm labor. Association with infection. J Clin Invest. 1990;85:1392–1400. doi: 10.1172/JCI114583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Menon R, Swan KF, Lyden TW, Rote NS, Fortunato SJ. Expression of inflammatory cytokines (interleukin-1ß and interleukin-6) in amniochorionic membranes. Am J Obstet Gynecol. 1995;172:493–500. doi: 10.1016/0002-9378(95)90562-6. [DOI] [PubMed] [Google Scholar]
- 7.Mitchell MD, Dudley DJ, Edwin SS, Schiller SL. Interleukin-6 stimulates prostaglandin production by human amnion and decidual cells. Eur J Pharmacol. 1991;192:189–191. doi: 10.1016/0014-2999(91)90090-d. [DOI] [PubMed] [Google Scholar]
- 8.Cox SM, Casey ML, MacDonald PC. Accumulation of interleukin-1beta and interleukin-6 in amniotic fluid:A sequela of labour at term and preterm. Hum Reprod Update. 1997;3:517–527. doi: 10.1093/humupd/3.5.517. [DOI] [PubMed] [Google Scholar]
- 9.Rajabi MR, Dean DD, Beydoun SN, Woessner JF., Jr Elevated tissue levels of collagenase during dilation of uterine cervix in human parturition. Am J Obstet Gynecol. 1988;159:971–976. doi: 10.1016/s0002-9378(88)80183-2. [DOI] [PubMed] [Google Scholar]
- 10.Winkler M, Rath W. Changes in the cervical extracellular matrix during pregnancy and parturition. J Perinat Med. 1999;27:45–61. doi: 10.1515/JPM.1999.006. [DOI] [PubMed] [Google Scholar]
- 11.Dudley DJ, Collmer D, Mitchell MD, Trautman MS. Inflammatory cytokine mRNA in human gestational tissues: Implications for term and preterm labor. J Soc Gynecol Investig. 1996;3:328–335. [PubMed] [Google Scholar]
- 12.Saito S, Kasahara T, Sakakura S, Umekage H, Harada N, Ichijo M. Detection and localization of interleukin-8 messenger RNA and protein in human placenta and decidual tissues. J Reprod Immunol. 1994;27:161–172. doi: 10.1016/0165-0378(94)90001-9. [DOI] [PubMed] [Google Scholar]
- 13.MacDonald PC, Casey ML. The accumulation of prostaglandins (PG) in amniotic fluid is an after effect of labor and not indicative of a role for PGE2 or PGF2α in the initiation of human parturition. J Clin Endocrinol Metab. 1993;76:1332–1339. doi: 10.1210/jcem.76.5.8496326. [DOI] [PubMed] [Google Scholar]
- 14.Cox SM, Casey ML, MacDonald PC. Accumulation of interleukin-1beta and interleukin-6 in amniotic fluid: A sequela of labour at term and preterm. Hum Reprod Update. 1997;3:517–527. doi: 10.1093/humupd/3.5.517. [DOI] [PubMed] [Google Scholar]
- 15.Zhong WW, Burke PA, Hand AT, Walsh MJ, Hughes LA, Forse RA. Regulation of cytokine messenger RNA expression in lipopolysaccharide-stimulated human macrophages. Arch Surg. 1993;128:158–163. doi: 10.1001/archsurg.1993.01420140035006. [DOI] [PubMed] [Google Scholar]
- 16.Hendricks CH, Brenner WE, Kraus G. Normal cervical dilatation pattern in late pregnancy and labor. Am J Obstet Gynecol. 1970;106:1065–1082. doi: 10.1016/s0002-9378(16)34092-3. [DOI] [PubMed] [Google Scholar]