OVERVIEW:
Prematurity accounts for 65% of perinatal morbidity after
the exclusion of congenital anomalies. Premature rupture of the fetal membranes (PROM) is associated with one third
of all preterm deliveries. Strong evidence links intraamniotic infection (IAI) and the subsequent occurance of
preterm labor (PTL) and PROM. IAI and the host inflammatory response can lead to the accumulation of pro-inflammatory
cytokines, many of which are known to induce the release of uterotonins from gestational tissues, thereby causing
uterine contraction and preterm labor. In vitro studies conducted in our laboratory have documented regulation
of inflammatory cytokine gene expression and release in human fetal membranes by interleukin-10 (IL-10), an immunomodulatory
cytokine.
ROLE OF INFLAMMATORY CYTOKINES IN PRETERM LABOR
(PTL)
- The work by Perinatal Research Center (PRC)and others (Romero
R, MacDonald PC, Casey LM, Mitchell MD, Hunt JS etc.) have documented the importance and central role of the inflammatory
cytokines in PTL.
- It is theorized by the PRC that PTL is a host response disease
induced by infection or other stimuli but caused by over release of cytokines and other host response agents.
- The PRC has shown that cytokines (IL-1 [interleukin-1] ,
IL-6, IL-8, IL-10, IL-15, IL-18, and TNF " are produced by the fetal membranes and go up in PTL (except IL-18).
- The membrane cytokine response mirrors that documented in
the amniotic fluid during intraamniotic infection (IAI).
- Inflammatory cytokines (IL-1, IL-6 ad TNF-") cause the
release of compounds (prostaglandins) which cause the uterus to contract.
- THIS LEADS TO PRETERM LABOR
IMMUNO-REGULATORY CYTOKINES CAN INHIBIT THE
INFLAMMATORY CYTOKINE PATHWAY
- IL-10 is one of the body's regulators of the inflammatory
cytokine pathway
- IL-10 is produced in the uterus in very low levels ( highest
documented level is 0.896 ng/ml).
- The PRC has shown that at high levels IL-10 can turn off
the entire pro-inflammatory cytokine pathway at the level of the gene!
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