Abnormal First Trimester Serum Interleukin 18 Levels are Associated with a Poor Outcome in Women with a History of Recurrent Miscarriage

Abstract

Increased levels of IL-18 appeared to be critical in early pregnancy and were able to discriminate between pregnancies that continued and those that end in 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 promotes inflammation indirectly by stimulating IL-1b expression, which by structurally resembling IL-18, binds IL-18 receptors and thus potentiates proinflammation (2, 3) by engaging similar signaling and signal transduction (2,4). Alterations of IL-18 have been investigated in the susceptibility to autoimmune and inflammatory disorders (4,5), and changes in IL-18 levels have been linked with pregnancy complications, including preeclampsia (6,7), preterm delivery (8), IVF-ET failure (9), implantation failure (4,10), and recurrent miscarriage (10)(11)(12).…”

“…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.…”

T Helper 1 and 2 Immune Responses in Relationship to Pregnancy, Nonpregnancy, Recurrent Spontaneous Abortions and Infertility of Repeated Implantation Failures

“…Elevated serum levels of IL-12, IL-18 and IFN-␥ have been reported in pregnant women with a history of RSA who miscarried the index pregnancy as compared to normal pregnant women and women with a history of RSA who delivered the index pregnancy [58]. In addition, it has been shown that first trimester IL-18 serum level distinguishes between successful and unsuccessful pregnancies [58]. Also, IL-18 in cervical mucus and amniotic fluid was higher in women with preterm labor than in those not in labor, at term.…”