Elevated Amniotic Fluid Nitrix Oxide Metabolites and Interleukin-6 in Intra-amniotic Infection

Objective: To compare amniotic fluid nitric oxide metabolites and interleukin-6 (IL-6) concentrations in paitents with and without intra-amniotic infection.

Methods: Amniotic fluid nitric oxide metabolites, IL-6, Gram stains, glucose, leukocyte counts, leukocyte esterase activity, creatinine, pH, and specific gravity were determined in 14 patients with intra-amniotic infection and 26 patients without intra-amniotic infection. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture. The nitric oxide metabolites, nitrate and nitrite (NO_x), were measured using Greiss reagent after reduction of nitrate to nitrite with aspergillus nitrate reductase. Interleukin-6 was measured by a two-site, enzyme-linked immunosorbent assay. Amniotic fluid nitric oxide metabolites and IL-6 concentrations were normalized by amniotic fluid creatinine levels. The Mann-Whitney U test, contingency table method, and Spearman's rank correlation test were used for statistical analyses.

Results: Amniotic fluid NO_x and IL-6 levels were significantly higher in patients with intra-amniotic infection than in those without intra-amniotic infection (NO_x: median = 2.06 μmol/mg creatinine, range = 0.74-6.81 versus 1.35 μmol/mg creatinine, range = 0.99-1.60, P = .01, IL-6: median = 2.00 μg/mg creatinine, range = 0.026-4.07 versus median = 0.04 μg/mg creatinine, range = 0.004-3.210, P = .0009, respectively). Patients with intra-amniotic infection had significantly elevated leukocyte counts, leukocyte esterase activity, Gram positive stains, and significantly lower amniotic fluid glucose levels compared with those without intra-amniotic infection. There were no differences in gestational age, maternal age, parity, race, pH, or specific gravity between the two groups. Amniotic fluid NO_x was significantly correlated with IL-6 (r = .4, P = .02). Both amniotic fluid NO_x and IL-6 were also positively correlated with amniotic fluid leukocyte counts, leukocyte esterase activity and Gram stains, and negatively correlated with glucose levels.

Conclusions: Amniotic fluid NO_x and IL-6 are significantly elevated and positively correlated during intra-amniotic infection. Both increased amniotic fluid IL-6 and nitric oxide may exert cytotoxic and cytostatic effects on the target cells. We suggest that measurements of amniotic fluid NO_x and IL-6 may serve as useful clinical markers in patients with intra-amniotic infection.