Identification of placental cytokine-producing cells in term and preterm labor

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Abstract
Objective: To determine if the production of proinflammatory cytokines by placentally derived macrophages changes with term and preterm labor and to examine if changes in antigen expression of these cytokines can be detected by immunohistologic methods. Methods: Enzymatically dispersed placental cell suspensions of the trophoblastic villi, obtained from 16 women with spontaneous term delivery, 16 women with elective cesarean delivery without any labor, and 22 preterm delivering women with labor unresponsive to tocolysis, were fractionated by magnetic-associated-cell-sorting, on the basis of CD11b-antigen expression. Positively and negatively sorted cell fractions were cultured and concentrations of interleukin-6, interleukin-1β, and tumor-necrosis-factor-α were measured in the culture supernatants. Immunohistologic staining was used for identification of cytokine-producing cells within placental tissues. Results: Positively sorted cells obtained from term (median 2027 pg/mL, P = .037) and preterm (median 3628 pg/mL, P = .001) laboring women produced significantly elevated amounts of tumor-necrosis-factor-α compared with non-laboring (median 1088 pg/mL) women at term. Negatively sorted cell fractions obtained from term (median interleukin-1β 162 pg/mL, P = .031, median interleukin-6 3134 pg/mL, P = .004) and preterm (median interleukin-1β 934 pg/mL, P = .003, median interleukin-6 5695 pg/mL, P = .001) laboring women produced significantly elevated amounts of interleukin-1β and interleukin-6 compared with nonlaboring (median interleukin-1β 29 pg/mL, median interleukin-6 135 pg/mL) women at term. Immunohistologic staining revealed that tumor-necrosis-factor-a activity was localized in isolated stromal cells, whereas interleukin-1β and interleukin-6 were predominantly found in endothelial cells within placental villi. Conclusion: The source of labor-associated release of tumor-necrosis-factor-α from placental tissues are macrophages, whereas interleukin-1β and interleukin-6 are released from placental endothelial cells.

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