Cytokine production by peripheral blood mononuclear cells of women with a history of preterm birth.

Preterm birth is associated with elevated production of pro-inflammatory cytokines such as TNFalpha at the maternal-fetal interface. Previous studies have suggested that women with a history of preterm birth produce aberrantly strong inflammatory responses to bacterial lipopolysaccharide (LPS). However many intrauterine infections in women are associated with pathogens including Ureaplasma urealyticum, Mycoplasma hominis and Streptococcus agalactiae (group B streptococcus) that contain pro-inflammatory factors other than LPS. We evaluated whether peripheral blood leukocytes from women with a history of preterm birth produce elevated amounts of TNFalpha upon stimulation with pathogens associated with preterm birth and if pre-treatment with aspirin, an anti-inflammatory medication, decreases the ex vivo production of this cytokine. Heat-killed bacteria elicited increased TNFalpha production from leukocytes in a dose-dependent manner, but no differences in TNFalpha production between leukocytes from women with preterm birth and control women with term birth were detected. In women who consumed aspirin each day for one week, TNFalpha production was increased in leukocytes from control women stimulated with Escherichia coli and U. urealyticum, but was reduced or unchanged in leukocytes from women with preterm birth. Similar trends were observed for a subset of samples stimulated with U. urealyticum and assayed for IL-6, IL-10, IL-1beta and TNFalpha by bead array. We conclude that leukocytes from women with a history of preterm birth do not have elevated pro-inflammatory responses to pathogens, and that reproductive history is associated with different effects of aspirin on pro-inflammatory cytokine production.

Effect of aspirin treatment on TNFalpha production by women with a history of preterm birth.

Lipopolysaccharide (LPS)-stimulated TNFalpha production is reported to be greater for whole blood (WB) cultures prepared from patients with a history of preterm birth than cultures obtained from women with a history of term birth. The objectives of this study were (1) to determine if there is a similar differential responsiveness for peripheral blood mononuclear leukocytes (PBML) and (2) to determine if treatment with aspirin influences LPS-stimulated TNFalpha production in these patients. WB and PBML were obtained from women with a history of preterm delivery before 32 weeks (cases; n=5) and age- and race-matched controls (n=5) with a history of uncomplicated term delivery. WB and PBML were cultured and stimulated with LPS. All participants then took aspirin daily for 1 week and responsiveness of PBML and WB cultures to LPS was retested. The history of preterm labor was found to have no effect on LPS-stimulated TNFalpha production in cultures of WB or PBML. Aspirin treatment enhanced LPS-stimulated TNFalpha production by PBML from controls but not cases. We conclude that endotoxin responsiveness of women with a history of preterm birth is similar to that of women with a history of term birth in terms of in vitro TNFalpha production. Aspirin increases TNFalpha production by PBML in control women but not in women with a history of preterm birth. The divergent responses to aspirin treatment in patients with and without prior preterm labor may reflect differential regulation of cytokine production by prostaglandins in women with preterm labor associated with infection or inflammation.

Changes in the isoforms of the sodium pump in the placenta and myometrium of women in labor.

OBJECTIVE: We determined whether changes in sodium pump isoform abundance accompanied active human labor. STUDY DESIGN: Specimens of placenta, amniochorion, and myometrium were collected from women in active spontaneous labor and from those not in labor. The abundance of the three sodium pump alpha-isoforms was determined by Western blot analysis. RESULTS: Levels of the alpha1 and alpha2 isoforms were comparable in the three tissues for women in labor and not in labor. However, alpha3 isoform abundance in placenta and myometrium (but not amniochorion) was significantly decreased in women in active labor compared with women not in labor (sodium pump alpha3 in placenta: no labor 91.2 +/- 27.6 vs labor 46.9 +/- 3.6 density units, P =.002. Sodium pump alpha3 in myometrium: no labor 52.3 +/- 7.7 vs labor 19.8 +/- 1.6 density units, P =.0002). CONCLUSION: Because reductions in sodium pump number can result in hormone release from secretory tissues and in contraction of muscle, this suggests that the sodium pump may play a significant role in the initiation or maintenance of human labor.