Objective:To determine if inflammatory cytokine mRNA in gestational tissues is present only in the setting of infection-associated preterm labor or under several other clinical conditions.
Methods:Human gestational tissues were collected from 51 women experiencing 1) term cesarean delivery without labor, 2) normal term vaginal delivery, 3) preterm cesarean delivery without labor, 4) preterm vaginal delivery without chorioamnionitis, and 5) preterm vaginal delivery with concomitant chorioamnionitis. Decidua, chorion, and amnion were isolated, total RNA from each tissue was extracted, and the presence of inflammatory cytokine mRNA was determined by polymerase chain reaction. Interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α mRNA was detected using specific oligonucleotide primers.
Results:Interleukin-1β mRNA was rarely found in tissues preterm without labor but was readily detected in both maternal and fetal tissues after labor, regardless of gestational age. Interleukin-6 mRNA was rare in tissues from the nonlaboring patient but was found in almost all tissues after labor. Interleukin-8 mRNA was detected in all tissues at term, both in nonlaboring and laboring patients. Tumor necrosis factor-α mRNA was detected in only 20-50% of tissues after labor, and was rarely detected in the absence of labor.
Conclusions:Inflammatory cytokine mRNA is commonly expressed in human gestational tissues after normal labor and preterm labor with or without associated intrauterine infection. There was no difference in the pattern of expression of mRNA inflammatory cytokine in women who did or did not have clinically evident intrauterine infection.
1. Romero R, Mazor M, Wu YK, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol1988;12:262-279.
2.
2. Romero R, Brody DT, Oyzrzun E, et al. Infection and labor. III. Interleukin-1: A signal for the onset of parturition. Am J Obstet Gynecol1989;160:117-123.
3.
3. Romero R, Manogue KR, Mitchell MD, et al. Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor. Am J Obstet Gynecol1989;161:336-341.
4.
4. Romero R, Avila C, Santhanam U, Sehgal P. Amniotic fluid interleukin-6 in preterm labor. J Clin Invest1990;85:1392-1400.
5.
5. Romero R, Ceska M, Avila C, Mazor M, Behnke E, Lindley I. Neutrophil attractant/activating peptide-l/interleukin-8 in term and preterm parturition. Am J Obstet Gynecol1991;165:813-820.
6.
6. Dudley DJ, Hunter C, Mitchell MD, Varner MW. Clinical value of amniotic fluid interleukin-6 determinations in the management of preterm labor. Br J Obstet Gynecol1994;101:592-597.
7.
7. Romero R, Yoon BY, Mazor M, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and Gram stain in patients in preterm labor with intact membranes. Am J Obstet Gynecol1993;169:805-816.
8.
8. Grieg PC, Ernest JM, Teot L, Erikson M, Talley R. Amniotic fluid interleukin-6 levels correlate with histologic choriamnionitis and amniotic fluid cultures in patients in premature labor and with intact membranes. Am J Obstet Gynecol1993;169:1035-1044.
10. Dudley DJ, Lundin-Schiller S, Edwin SS, Trautman MS, Mitchell MD. Biosynthesis of interleukin-6 by cultured human chorion laeve cells: Regulation by cytokines. J Clin Endocrinol Metabol1992;75:1081-1086.
11.
11. Dudley DJ, Trautman MS, Mitchell MD. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: Evidence for a cytokine network at the chorio-decidual interface. J Clin Endocrinol Metabol1993;76:404-410.
12.
12. Matsuzaki N, Taniguchi T, Shimoya K, et al. Placental interleukin-6 production is enhanced in intrauterine infection but not in labor. Am J Obstet Gynecol1993;168:94-97.
13.
13. Shimoya K, Matsuzaki N, Taniguchi T, et al. Human placenta constitutively produces interleukin-8 during pregnancy and enhances its production in intrauterine infection. Biol Reprod1992;47:220-226.
14.
14. Trautman SM, Dudley DJ, Edwin SS, et al. Amnion cell biosynthesis of interleukin-8: Regulation by inflammatory cytokines. J Cell Physiol1992;153:38-43.
15.
15. Menon R, Swan KF, Lyden TW, Rote NS, Fortunato SJ. Expression of inflammatory cytokines (interleukin-1β and interleukin-6) in amnoochorionic membranes. Am J Obstet Gynecol1995;172:493-500.
16.
16. Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intra-amniotic infection. Am J Obstet Gynecol1991;164:1317-1326.
17.
17. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Annal Biochem1987;162:156-159.
18.
18. Maniatis P, Fritsh EF, Sambrook J. Molecular cloning—a laboratory manual. Cold Spring Harbor. New York: Cold Spring Harbor Laboratory, 1982.
19.
19. March CJ, Mosby B, Larsen A, et al. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature1985;315:641-647.
20.
20. May LT, Helfgott DC, Sehgal PB. Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: Structural studies of the beta 2 interferon involved. Proc Natl Acad Sci USA1986;83:8957-8961.
21.
21. Matsushima K, Morishita K, Yoshimura T, et al. Molecular cloning of a human monocyte derived neutrophis chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med1988;167:1883-1893.
22.
22. Wang AM, Creasey AA, Lader MB, et al. Molecular cloning of the complementary DNA for human tumor necrosis factor. Science1985;228:149-154.
23.
23. Kanno H, Huang IY. Kau YW, Yoshida A. Structural genes on different chromosomes are required for encoding the major subunit of human red cell glucose-6-phosphate dehydrogenase. Cell1989;58:595-606.
24.
24. Lundin-Schiller S, Mitchell MD. Prostaglandin production by human chorion laeve cells in response to inflammatory mediators. Placenta1991;12:353-363.
25.
25. Mitchell MD, Edwin SS, Romero RJ. Prostaglandin biosynthesis by human decidual cells: Effects of inflammatory mediators. Prostaglandins Leukot Essent Fatty Acids1990;41:35-38.
26.
26. Romero R, Durum S, Dinarello C, Oyarzun E, Hobbins JC, Mitchell MD. Interleukin-1 stimulates prostaglandin biosynthesis by human amnion. Prostaglandins1989;37:13-22.
27.
27. Mitchell MD, Edwin SS, Lundin-Schiller S, Silver RM, Smotkin D, Trautman MS. Mechanism of interleukin-1μ stimulation of human amnion prostaglandin biosynthesis: Mediation via a novel inducible cyclooxygenase. Placenta1993;14:615-625.
28.
28. Mitchell MD, Dudley DJ, Edwin SS, Schiller SL. Interleukin-6 stimulates prostaglandin production by human amnion and decidual cells. Eur J Pharmacol1991;192:189-191.
29.
29. Lundin-Schiller S, Mitchell MD. The role of prostaglandins in human parturition. Prostaglandins Leukot Essent Fatty Acids1990;39:1-10.
30.
30. Mitchell MD, Trautman MS, Dudley DJ. Cytokine networking in the placenta. Placenta1993;14:249-275.
31.
31. Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv Immunon1994;55:97-179.
32.
32. Kanayama N, Terao T. The relationship between granulocyte elastase-like activity of cervical mucus and cervical maturation. Acta Obstet Gynecol Scand1991;70:29-34.
33.
33. Osmers RGW, Blaser J, Kuhn W, Tschesch H. Interleukin-8 synthesis and the onset of labor. Obster Gynecol1995;86:223-229.
34.
34. MacDonald PC, Koga S, Casey ML. Decidual activation in parturition: Examination of amniotic fluid for mediators of the inflammatory response. Ann NY Acad Sci1991;622:315-330.
