The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition

OBJECTIVE: The common terminal pathway of parturition describes the anatomi c, biochemical, endocrine, and clinical events present in the fetus and mot her in both term and preterm labor. Labor at term is thought to result from physiologic activation of this pathway, whereas preterm labor is the resul t of pathologic activating events. The purpose of this study was to determi ne whether physiologic and pathologic activation could be discerned by the analysis of a cytokine-receptor signaling system. Tumor necrosis factor alp ha and its soluble receptors were used as probes because of their pivotal r ole in the regulation of several processes activated during parturition. So luble receptors are thought to buffer the biologic and potentially deleteri ous effects of tumor necrosis factor alpha in pathologic conditions. STUDY DESIGN: The in vivo concentrations of tumor necrosis factor alpha and its soluble receptors were studied in patients in term labor and preterm l abor. Amniotic fluid was retrieved from 175 women and tumor necrosis factor alpha, tumor necrosis factor receptor 1, and tumor necrosis factor recepto r 2 concentrations were measured by highly sensitive immunoassays. Patients were classified in the following groups: (1) term labor (n = 29), (2) term not in labor (n = 29), (3) preterm labor leading to term delivery (n = 34) , (4) preterm labor without infection resulting in preterm delivery (n = 34 ), (5) preterm labor with intra-amniotic infection (n = 23), and (6) second trimester (n = 26). RESULTS: Tumor necrosis factor alpha and tumor necrosis factor receptor 1 c oncentrations decreased with advanced gestational age (r = -0.51 and r = -0 .7; P < .01 for each). (1) Patients in Spontaneous term labor had a higher median concentration of tumor necrosis factor alpha than those at term not in labor (median; 6.4 pg/mL; range, 2.4->500 pg/mL vs median, 4.1 pg/mL; ra nge, 1.1-22.7 pg/mL; P < .01) but had lower concentrations of tumor necrosi s factor receptor 1 (median, 3.2 ng/mL; range, 1.3-9.1 ng/mL vs median, 4.2 ng/mL; range, 1.6-8.3; P < .001) and tumor necrosis factor receptor 2 (med ian, 5.5 ng/mL; range, 0.73-12.8 ng/mL vs median, 6.8 ng/mL; range, 2.9-12. 9 ng/mL; P < .01). (2) In contrast, patients with preterm labor leading to preterm delivery had higher concentrations of tumor necrosis factor alpha ( median, 12.3 pg/mL; range, 1.5->500 pg/mL vs median, 4.8 pg/mL; range, 1-60 .9 pg/mL; P < .01), tumor necrosis factor receptor 1 (median, 8.8 ng/mL; ra nge, 2.5-38 ng/mL vs median, 6.2 ng/mL; range, 1.4-28 ng/mL; P < .05), and tumor necrosis factor receptor 2 (median, 8.5 ng/mL; range, 3.5-45.4 ng/mL vs median, 6.1 ng/mL; range, 1.99-14.1 ng/mL; P < .01) than patients with p reterm labor who delivered at term. (3) Microbial invasion of the amniotic cavity was associated with dramatic increases in the concentrations of tumo r necrosis factor alpha (median, 93.5 pg/mL; range, 1.2->500 pg/mL) and its soluble receptors tumor necrosis factor receptor 1 (median, 8.8 ng/mL; ran ge, 2.1-36.7 ng/mL) and tumor necrosis factor receptor 2 (median, 11.8 ng/m L; range, 3.4-46.3 ng/mL), concentrations that were significantly higher th an in those with preterm labor who delivered at term and those who delivere d preterm but were nor infected. CONCLUSION: The tumor necrosis factor alpha and tumor necrosis factor alpha soluble receptor profiles are different in term and preterm parturition. O ur observations provide support for the thesis that preterm parturition is a pathologic condition. Increased tumor necrosis factor alpha soluble recep tor concentrations may attenuate the deleterious effects of the excess of t umor necrosis factor alpha found in pathologic labor.