Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection

Objectives: To evaluate the role of interleukins (IL-1, IL-6), tumor necrosis factor α (TNFα) and for the first time interferon gamma (IFNγ) and epidermal growth factor (EGF) in the pathogenesis of premature rupture of membranes (PROM) with and without confirmed intrauterine infection. Methods: Amniotic fluid was retrieved by transabdominal amniocentesis from 30 patients with PROM and 20 normal pregnant women with intact membranes of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma whether or not clinical signs of chorioamnionitis were present. Maternal serum and amniotic fluid IL-1, IL-6, TNFα and IFNγ concentrations were determined by the corresponding immunoradiometric assay, whereas EGF concentration was determined by a specific radioimmunoassay. Results: Nearly all cases of PROM with infection revealed elevated amniotic fluid cytokines (IL-1β, IL-6, TNFα, IFNγ, EGF) whereas half of them revealed elevated serum cytokines. In cases of PROM without confirmed infection, there were no significant changes of maternal serum cytokines, whereas two-thirds of them revealed elevated amniotic fluid cytokines. Conclusions: The rise of cytokines in amniotic fluid of cases of PROM with infection may represent: (a) enhanced macrophage activity for immunosurveillance of the fetus; (b) a preparatory step for the initiation of labor; and (c) a valuable tests for diagnosing chorioamnioitis. The mechanism responsible for PROM in the presence or absence of infection is likely to be of different nature.