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Keywords:

  • Cytokines;
  • intrauterine infection;
  • human parturition

PROBLEM: This study was conducted to determine whether: (1) gestational age, parturition, and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of immunoreactive macrophage inflammatory protein-1α; (2) amniotic fluid concentrations of macrophage inflammatory protein-1α are correlated with the white blood cell count and the concentrations of interleukin-8 in amniotic fluid.

METHOD: Amniotic fluid was retrieved by amniocentesis from 126 patients; 54 women with preterm labor and intact membranes (no MIAC-delivery at term, N = 21; no MIAC-preterm delivery, N = 16; MIAC-preterm delivery, N = 17); 62 patients at term (no labor, N = 19; labor-no MIAC, N = 20; labor-MIAC, N = 23); and 10 patients in the midtrimester of pregnancy. Amniotic fluid was cultured for aerobic, anaerobic and Mycoplasma species. Determinations of amniotic fluid macrophage inflammatory protein-1α and interleukin-8 were performed with immunoassays validated for amniotic fluid (sensitivity: 14.2 pg/ml and 0.3 ng/ml, respectively). Kruskal-Wallis analysis of variance (ANOVA) for censored data, Mann-Whitney U test and Spearman's rank correlation were performed for analysis.

RESULTS: 1) Amniotic fluid macrophage inflammatory protein-1α was present in only 31.0% (9/29) of patients not in labor (midtrimester and term). 2) Patients with preterm labor and MIAC had higher amniotic fluid concentrations of macrophage inflammatory protein-1α than those without MIAC (no MIAC-delivery at term: median 0.0 pg/ml, range 0.0–221.2; no MIAC-preterm delivery: median 37.4 pg/ml, range 0.0–494.6; MIAC-preterm delivery: median 7171.0 pg/ml, range 402.5–37994.0; P<0.00001). 3) Among patients at term, MIAC was associated with higher concentrations of amniotic fluid macrophage inflammatory protein-1α than patients without MIAC (no labor: median 0.0 pg/ml, range 0.0–25.6; labor-no MIAC: median 16.7 pg/ml, range 0.0–161.6; labor-MIAC: median 103.8 pg/ ml, range 0.0–4349.0, P<0.001). 4) Among patients in preterm labor, a strong correlation was found between amniotic fluid concentrations of macrophage inflammatory protein-1α and interleukin-8 (r = 0.9, P<0.00001) and between amniotic fluid macrophage inflammatory protein-1α concentrations and amniotic fluid white blood cell count (r = 0.6, P<0.0001).

CONCLUSIONS: (1) Macrophage inflammatory protein-1α is undetectable in most amniotic fluid samples from patients in the midtrimester of pregnancy and at term not in labor. (2) Microbial invasion of the amniotic cavity is associated with increased concentrations of immunoreactive amniotic fluid macrophage inflammatory protein-1α in both term and preterm gestations. (3) Amniotic fluid macrophage inflammatory protein-1α concentrations significantly correlate with interleukin-8 levels and white blood cell count in amniotic fluid. Our data strongly suggest a role for macrophage inflammatory protein-1α in the mechanisms responsible for the recruitment of leukocytes into the amniotic cavity during the course of intrauterine infection.