Neutrophil elastase and secretory leukocyte protease inhibitor in prelabor rupture of membranes, parturition and intra-amniotic infection

Abstract

Objective: Neutrophil elastase (NE), a multifunctional serine protease stored in azurophilic granules of mature neutrophils, is capable of intracellular degradation of proteins during phagocytosis and extracellular degradation of connective tissue during an inflammatory process. Secretory leukocyte protease inhibitor (SLPI) is a natural NE inhibitor present in amniotic fluid, fetal membranes and cervical mucus. An imbalance between NE and SLPI has been implicated as a mechanism of abnormal tissue destruction in chronic inflammatory diseases. The purpose of this study was to determine if parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of NE and SLPI. Study design: Amniotic fluid was retrieved by amniocentesis from 380 patients in the following groups: (1) preterm labor and intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 13) or prematurely (n = 26), and preterm labor with microbial invasion of the amniotic cavity (n = 9); (2) preterm PROM with (n = 34) and without (n = 51) microbial invasion of the amniotic cavity; and (3) term gestation without microbial invasion of the amniotic cavity with intact membranes not in labor n = 63), in labor (n = 158), and with rupture of membranes not in labor (n = 26). Microbial invasion of the amniotic cavity was determined by a positive amniotic fluid culture for micro-organisms including aerobic, anaerobic and Mycoplasma species. NE and SLPI amniotic fluid levels were determined by highly specific and sensitive immunoassays. Results: Preterm PROM was associated with a significant increase in the amniotic fluid concentration of NE. Microbial invasion of the amniotic cavity was associated with a significant increase in the amniotic fluid concentration of NE in women with preterm labor and intact membranes, as well as in women with preterm PROM. Term and preterm parturition was associated with a significant increase in the amniotic fluid concentration of NE. In the absence of microbial invasion of the amniotic cavity, preterm and term PROM were associated with a significant reduction in the amniotic fluid concentration of SLPI. Conclusion: Preterm PROM, microbial invasion of the amniotic cavity, and parturition at term and preterm are associated with a significant increase in the amniotic fluid concentration of NE. PROM is associated with a reduced amniotic fluid concentration of SLPI.