Dose down regulation of tumor necrosis factor - prevent preterm labor?

ABSTRACT

Labor at term is thought to result from physiologic activation of anatomic, biochemical, and endocrine pathways. Whereas preterm labor result from pathologic activation of such events. The purpose of this study was to determine whether physiologic and pathologic activation could be described by the analysis of a cytokine-receptor signaling system. Tumor necrosis factor alpha [TNF-alpha.] and its soluble receptors [TNF-R1 and TNF-R2] were used as probes because of their role in the regulation of several processes activated during parturition.The in vivo concentrations of TNF-alpha and its soluble receptors were assayed in amniotic fluid obtained from 150 women, classified into 5 groups [each includcd 30] Group-A consisted of women at term with intact memberanes not in labor, group B women with intact memberanes and in labor, group I women with preterm labor and intact. memberanes who delivered at term with no evidence of infection, group 2 women with preterm labor who delivered prematurely in the absence of chorio-amnionitis, and group 3 consisted of women with preterm labor and proven microbial invasion of the amniotic cavity who delivered preterm neonates women in spontaneous term labor [group-B] had significantly higher median concentrations of TNF-alpha a lower TNF-R1 and TNF-R2 than those at term not in labor [group-A]. Meanwhile, women with preterm labor leading to preterm delivery [group 2] had significantly higher concentrations of TNF-alpha. TNF-R1 and TNF-R2 than those with premature labor leading to term delivery [group 1]. On other hand, microbial invasion of the amniotic cavity [group 3] was associated with dramatic increases in the concentration of TNF-alpha and its soluble receptors than in those with preterm labor who delivered at term and those who delivered preterm but were not infected. It is concluded that levels of TNF-alpha and its soluble receptors, in the amniotic fluid, are different in term and preterm parturition, and that preterm parturition and/or microbial invasion of the amniotic cavity are pathologic conditions associated with increased TNF-alpha receptors which attenuate the deleterious effects of TNf-alpha found in. pathologic labor. It is concluded that the administration of TNF-alpha receptors to mothers at risk of pathologic preterm labor may be beneficial