Abnormal cytokine levels in non-pregnant women with a history of recurrent miscarriage

Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage

“…Serum IL-18 levels were significantly lower in patients than in control women. This was reminiscent of previous findings documenting reduced IL-18 levels in patients experiencing miscarriage (21), suggesting that increased IL-18 levels are critical in early pregnancy (12,13) and that changes in IL-18 levels may discriminate between successful pregnancies and miscarriages (12) and determine the outcome of subsequent pregnancies, as was suggested (21). However, this is an oversimplification given the wide range of serum IL-18 values seen here (20.2-1,485.7 pg/mL for patients and 45.1-1,837.9 pg/mL for control women) and elsewhere (21) and the sequential expression of cytokines in uterine, decidual, and placental tissues at distinct stages in pregnancy (13,36).…”

“…Functionally, both variants were linked with reduced IL-18 availability, evidenced by a progressive reduction in serum IL-18 levels in heterozygous and homozygous carriers in both patients and control women. These findings underscore the significance of reduced IL-18 levels in the maintenance of normal pregnancy (12,21), and in the pathogenesis of pregnancy complications (6,8,28), including RSM (21).…”

“…IL-18 is expressed by epithelial cells of the amnion, chorionic cells, and decidual cells but not by syncytiotrophoblasts of the villi, and altered IL-18 levels have been linked to increased RSM risk (10)(11)(12)21). Insofar as IL-18 promoter singlenucleotide polymorphisms (SNPs) are associated with differential expression of IL-18 (22), this suggests a genetic susceptibility of RSM based on IL-18 promoter variants or haplotypes.…”

Circulating levels of cytokines during pregnancy: thrombopoietin is elevated in miscarriage

“…Other traditional Th1 and Th2 cytokines, such as IL-2 and IL-10, were not detected in our preliminary study and thus not included in this investigation. Previous reports have suggested a "Th2 bias" in successful pregnancy (11,18,20,22,(37)(38)(39), but results from human studies have not uniformly been in agreement; some have yielded null findings (5,23,40-42) and others observed a protective effect of certain Th1 cytokines (41,42). A possible explanation for inconsistency in human studies may be related to timing of sample collection relative to the miscarriage.…”

Interleukin‐18 and gestosis: correlation with Helicobacter pylori seropositivity

“…Moreover increased levels of IL-18 have been observed in serum and organic fluids of women suffering from gynecologic pathologies, such as polycystic ovary syndrome 4 and endometriosis. 5 In contrast, low circulating levels of IL-18 were reported in non-pregnant women with a history of recurrent miscarriage by Wilson et al (2004) 6 and according to Adams et al (2003) In particular, in this brief report we analyze the role of IL-18 in a population of pre-eclamptic women with high seroprevalence for pathogenic strains of H. pylori. In fact, also in an experimental model in mice, H. pylori infection negatively influences pregnancy, inducing macrophage activation and T lymphocytes stimulation, especially Th1 ones.…”