Diagnostic biomarkers of pro-inflammatory immune-mediated preterm birth.

PURPOSE: Pro-inflammatory immunity, either infectious or sterile-derived, is one of the major causes of preterm birth and associated with enhanced maternal and fetal morbidity and mortality. Diagnosing intrauterine inflammation at an early stage is tremendously important. Amniotic fluid interleukin (IL)-6 concentration is currently the most investigated diagnostic tool for detecting intrauterine inflammation. METHODS: Amniotic fluid samples were obtained from women with no signs of intrauterine infection [amniocentesis (n = 82), cesarean section (n = 110), spontaneous delivery (n = 20) and those with clinical signs of intrauterine infection or inflammation (AIS, n = 16)]. Amniotic fluid was screened by commercial ELISAs for IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, growth regulated oncogene-α (gro) α, macrophage inflammatory protein (MIP) 1α, MIP1ß, histone, tumor necrosis factor (TNF) α, proIL1ß and interferon γ-induced protein (IP) 10. RESULTS: ProIL-1ß, MIP1ß, IL-10 and IL-8 levels were significantly elevated in the AIS group, whereas IL-4 levels were significantly lower in the AIS group. No significant differences were found regarding IL-2, IL-6, IL-12, IL-15, IL-17, GROα, MIP1α, histone, TNFα, ProIL1ß and IP10. CONCLUSION: MIP1ß, IL-4, IL-8, IL-10 and proIL-1ß might be potential singular biomarkers in diagnosing intrauterine inflammation. The combinations of elevated levels of IL-17/GROα, MIP1ß/IL-15 and histone/IL-10 are new potentially advantageous biomarker combinations.

Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid.

BACKGROUND: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. FINDINGS: Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age. CONCLUSION: Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.