Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor.

Abstract

This study was conducted as part of an investigation to evaluate the hypothesis that bacterial toxins (LPS or lipoteichoic acid), acting on macrophage-like uterine decidua to cause increased formation of cytokines, may be involved in the pathogenesis of infection-associated preterm labor. We found that cachectin/tumor necrosis factor-a (TNF-a) was synthesized and secreted into the culture medium by human decidual cells and explants in response to treatment with LPS. LPS treatment also caused an increase in PGF2a production by decidual cells and explants. In amnion cells in monolayer culture, TNF-a stimulated PGE2 formation, and TNF-a was cytostatic (inhibited [Hjthymidine incorporation into DNA) but not cytolytic in amnion cells. TNF-a was not detectable (< 0.34 ng/ml) in the amniotic fluid of normal pregnancies at midtrimester or at term before or after the onset of labor (n = 44); but TNF-a was present at concentrations between 2.8 and 22.3 ng/ml in amniotic fluids of 4 of 20 pregnancies with intact membranes complicated by preterm labor (< 34 wk gestational age). LPS was present in 10 of the 20 amniotic fluids of preterm labor pregnancies, including all four in which TNF-a was present. Bacteria were identified in only one of the four LPS-positive, TNF-a-positive fluids. Cytokine formation in macrophage-like decidua may serve a fundamental role in the pathogenesis of preterm labor, including increased prostaglandin formation and premature rupture of the membranes.

Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

“…When the DMs were stimulated with LPS, there was a considerable amount of TNF-a production by CD14 þ cells which peaked at 4 h, consistent with the results previously obtained using monocytes (Henter et al 1988). TNF-a has previously been shown to be constitutively produced in the decidua and its secretion by decidual cell suspensions has been shown to be enhanced by LPS (McGregor et al 1988, Casey et al 1989, Romero et al 1989, Vince et al 1992. The decidua comprises several cell types, but our present study shows that DMs are the major decidual cell type producing TNF-a in response to LPS challenge.…”

“…Pathogens such as Group B Streptococcus, Escherichia coli (E. coli), Neisseria gonorrhoeae and Chlamydia trachomatis are known to cause chorioamnionitis during pregnancy. Bacterial lipopolysaccharide (LPS) introduced into amniotic fluid can stimulate DMs to generate phospholipase A 2 and, hence, increased production of prostaglandins E 2 and F 2a (Casey et al 1989) which may lead to preterm labour. DMs may also produce cytokines such as IL-1, TNF-a and IL-6 in response to an infection and therefore cause an intrauterine inflammatory reaction that could provoke preterm parturition (McGregor et al 1988).…”

Tumor Necrosis Factor-α and Interleukin-1β Regulate Interleukin-8 Expression in Third Trimester Decidual Cells

“…The choriodecidua proved more responsive than the amnion. 35 Observations that LPS targets decidual cells and decidual macrophages to secrete TNF-␣ and IL-1␤ 33,[35][36][37] constitute the initial steps of the scheme of infectioninduced PPROM depicted in Figure 8. The current study provides the next step in the proposed scheme by demonstrating that both cytokines enhance IL-8 expression in term decidual cells.…”

Critical Paracrine Interactions Between TNF-α and IL-10 Regulate Lipopolysaccharide-Stimulated Human Choriodecidual Cytokine and Prostaglandin E2 Production

“…In tissues with histological chorioamnionitis, the chorion and decidua become infiltrated with leukocytes, which in some cases accumulate at the margin between the amnion and chorion (37). There is little doubt that the cytokines released by choriodecidual membranes upon LPS stimulation play a role in the elaboration of the inflammatory response; however, whether they are principal drivers of the inflammatory reaction or secondary modulators has been a matter for debate (38). Because both positive and negative regulators of the inflammatory reaction are produced in response to infection, the degree of stimulation observed would presumably depend upon the balance of pro/antiinflammatory cytokines released in response to contact with microbial products, which in this study was modeled using a bacterial LPS preparation from Escherichia coli.…”