interleukin-8 and Pregnancy--Ectopic

Unless an ectopic pregnancy is visible by ultrasound, diagnosis can be a challenge. Differentiating ectopic pregnancies from intrauterine pregnancies can be impossible without intervention or follow-up. This poses a clinical dilemma to the practitioner given the inherent danger to the mother of tubal rupture of an ectopic pregnancy versus the fear of intervening in the case of a desired pregnancy without certainty of diagnosis. Early diagnostic modalities are clearly lacking, and serum biomarkers are currently being investigated as a solution to need for a rapid and accurate test for ectopic pregnancy.

Topics: Activins; ADAM Proteins; ADAM12 Protein; Biomarkers; CA-125 Antigen; Chorionic Gonadotropin; Creatine Kinase; Estradiol; Female; Glycodelin; Glycoproteins; Humans; Inhibins; Interleukin-6; Interleukin-8; Leukemia Inhibitory Factor; Membrane Proteins; Myoglobin; Myosin Heavy Chains; Placental Lactogen; Pregnancy; Pregnancy Proteins; Pregnancy-Associated Plasma Protein-A; Pregnancy-Specific beta 1-Glycoproteins; Pregnancy, Ectopic; Progesterone; Proteome; Relaxin; Renin; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Ectopic pregnancy is a very dangerous complication of pregnancy, affecting 1%-2% of all reported pregnancies. Due to ethical constraints on human biopsies and the lack of suitable animal models, there has been little success in identifying functionally important genes in the pathogenesis of ectopic pregnancy. In the present study, we developed a random walk-based computational method named TM-rank to prioritize ectopic pregnancy-related genes based on text mining data and gene network information. Using a defined threshold value, we identified five top-ranked genes: VEGFA (vascular endothelial growth factor A), IL8 (interleukin 8), IL6 (interleukin 6), ESR1 (estrogen receptor 1) and EGFR (epidermal growth factor receptor). These genes are promising candidate genes that can serve as useful diagnostic biomarkers and therapeutic targets. Our approach represents a novel strategy for prioritizing disease susceptibility genes.

Topics: Algorithms; ErbB Receptors; Estrogen Receptor alpha; Female; Gene Regulatory Networks; Genetic Predisposition to Disease; Humans; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy, Ectopic; Vascular Endothelial Growth Factor A

Anti-Chlamydial trachomatis (anti-CT) responses, particularly anti-heat shock 60 (Hsp60), antibodies confer a higher risk of ectopic pregnancy. With emerging evidence supporting the pivotal role of interleukin-1β (IL-1β) and IL-8 in the immunopathogenesis of CT-specific tubal obstruction, we determined anti-CT Hsp60 antibody reactivity and serum concentrations of IL-1β and IL-8 in failed pregnancies consisting of 30 consecutive ectopic pregnancies and 30 missed abortions, with 32 viable intrauterine pregnancies tested as normal controls. ELISAs were utilised to measure IgA or IgG anti-CT major outer membrane outer protein (MOMP) antibodies, IgG anti-CT Hsp60 antibodies and IL-1β and IL-8. IgG anti-CT Hsp60 antibodies were more prevalent in ectopic pregnancy cases (43.3%, 13/30) than in intrauterine pregnancies (16%, 5/32, p=0.016). All 13 ectopic pregnancy anti-CT Hsp60-positive cases had anti-CT MOMP antibodies. CT-specific antibodies were more frequent in merged ectopic pregnancy and missed abortions cases (35%, 21/60) than in intrauterine pregnancies (16%, p=0.049). The median (range) levels of IL-1β in ectopic pregnancy, missed abortions and normal intrauterine pregnancies were 1.74 (0.2-8.7), 1.14 (0.2-16) and 1.22 (0.2-16.2) pg/ml, respectively (p>0.05, for all). Serum IL-8 levels were comparable amongst groups: ectopic pregnancy (median [range]: 25.1 [18.3-1000]); missed abortions (32.9 [15.39-1000]); and intrauterine pregnancies (25.11 [18.3-1000] pg/ml). Anti-CT antibody-positive ectopic pregnancy had significantly lower IL-1β levels (1.29 [0.2-2.93]) pg/ml than sero-negative ectopic pregnancy cases (2.09 [1.10-8.70]) pg/ml, (p=0.022), but IL-8 did not differ. Our data demonstrate that anti-CT Hsp60 immunity is a predominant feature of ectopic pregnancy. We conclude that neither IL-1β nor IL-8 can be considered markers of failed pregnancy, although lower levels of the former cytokine are associated with CT-related ectopic pregnancy.

Topics: Abortion, Missed; Adult; Antibodies, Bacterial; Bacterial Proteins; Biomarkers; Chaperonin 60; Chlamydia trachomatis; Female; Humans; Immunity, Humoral; Interleukin-1beta; Interleukin-8; Middle Aged; Porins; Pregnancy; Pregnancy, Ectopic; Prospective Studies; Risk; Trachoma; Young Adult

To determine whether early measurement of the serum cytokines interleukin-2 receptor (IL-2R), IL-6, and IL-8 along with human chorionic gonadotropin (hCG) and progesterone (P(4)) can differentiate an ectopic from an intrauterine gestation.. Retrospective analysis.. University-based fertility center.. 75 women who underwent treatment with in vitro fertilization (IVF) and subsequently had an ectopic gestation (n = 15), spontaneous abortion (SAB) (n = 30), or term delivery (TD) (n = 30).. Serum samples were obtained 14 (day 28) and 21 (day 35) days after oocyte retrieval.. Serum concentrations of IL-2R, IL-6, IL-8, P(4), and hCG.. Median hCG readings on day 28 and day 35 were statistically significantly lower in the ectopic gestation group than in those with spontaneous abortion or term delivery. On day 28, median IL-8 levels were lower in the ectopic gestation group when compared with all intrauterine gestations combined. No statistically significant differences in IL-2R or IL-6 levels were noted between groups. Despite P(4) supplementation, median day-35 P(4) levels were lower in ectopic gestation than in the spontaneous abortion and term delivery cycles.. In the setting of a rise or plateau in hCG levels, low day-28 IL-8 and day-35 P(4) levels suggested an extrauterine implantation. This assay combination may facilitate earlier diagnosis of an ectopic gestation when pregnancy location is unclear.

Topics: Abortion, Spontaneous; Adult; Biomarkers; Chorionic Gonadotropin; Embryo Implantation; Female; Fertilization in Vitro; Gestational Age; Humans; Interleukin-6; Interleukin-8; Live Birth; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy, Ectopic; Progesterone; Receptors, Interleukin-2; Retrospective Studies; Time Factors; Up-Regulation

To investigate the diagnostic relevance of serum cytokine concentrations in ectopic pregnancy (EP).. Cohort study.. University hospital.. Seventeen women with EP, 22 women with miscarriage, and 33 women with normal intrauterine pregnancy, at comparable stages of gestation.. Interleukin (IL)-2 receptor, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) determination by immunoradiometric assay.. Serum concentrations of progesterone, beta-hCG, IL-2R, IL-6, IL-8, and TNF-alpha.. Serum levels of IL-6 were higher in women with EP than in those with miscarriage and normal pregnancy. Serum levels of TNF-alpha were higher in women with EP than in those with miscarriage and normal pregnancy. Serum levels of IL-8 were higher in women with EP than in those with miscarriage and normal pregnancy. An IL-8 cutoff of >40 pg/mL predicted EP with a sensitivity of 82.4%, a specificity of 81.8%, and positive and negative predictive values of 58.3% and 93.8%. No difference in serum IL-2R levels was found among the groups.. Serum IL-8, IL-6, and TNF-alpha concentrations are higher in women with EP than in those with miscarriage and normal pregnancy. Further studies are needed to determine their diagnostic value.

Topics: Abortion, Spontaneous; Chorionic Gonadotropin; Cohort Studies; Female; Gestational Age; Humans; Interleukin-6; Interleukin-8; Predictive Value of Tests; Pregnancy; Pregnancy, Ectopic; Progesterone; Receptors, Interleukin-2; ROC Curve; Sensitivity and Specificity; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Ultrasonography