Genetic markers for preeclampsia in Peruvian women / Marcadores genéticos de preeclampsia en mujeres peruanas

Abstract Background: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. Objective: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1β-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. Methods: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. Results: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1β gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. Conclusion: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele.

Resumen Antecedentes: La preeclampsia es un trastorno multiorgánico asociado con la morbi-mortalidad materna y perinatal. En el Perú, su incidencia es del 10% y causa el 22% de las muertes maternas. Se encontró una asociación entre la preeclampsia y ciertos polimorfismos. Objetivo: Determinar asociación entre los polimorfismos genéticos del factor de crecimiento endotelial vascular (VEGF) +936 C/T y +405 G/C, interleucina-6 (IL-6) -174G/C, IL-1β -511 C/T, Apo A-1 -75 G/A, Apo B-100 2488 C/T (Xbal), y preeclampsia en gestantes peruanas. Métodos: Se incluyeron gestantes preeclámpticas y sanas (controles). Las muestras de sangre fueron procesadas para extracción del ADN, y el análisis se realizó con la técnica PCR-RFLP con protocolos específicos para cada gen y confirmación con secuenciamiento Sanger. Se compararon las frecuencias alélicas y genotípicas en los casos (preeclampsia) y los controles. Resultados: No se halló asociación entre los polimorfismos VEGF+936-C/T y VEGF+405 y la preeclampsia. Las frecuencias de los genotipos GG y el alelo G del polimorfismo -174-G/C en el gen IL6 en preeclámpticas y controles, mostraron diferencias significativas, con frecuencias más altas en los casos. Para el polimorfismo -511-C/T del gen IL-1β, no se encontraron diferencias significativas en las frecuencias de genotipos TT comparados con CT+CC. Los genotipos y alelos de las variantes Apo-A1-75-G/A y Apo-B100 Xbal no mostraron diferencias significativas entre los grupos Conclusión: No se encontró asociación entre los marcadores genéticos estudiados y la preeclampsia. Sin embargo, el polimorfismo -174-G/C en el gen IL6 mostró diferencias significativas principalmente en el genotipo GG y el alelo G.

Interleukin-6 and interleukin-10 plasma levels and mRNA expression in polytrauma patients / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>Host response to polytrauma occasionally has unpredictable outcomes. Immune response is a major factor influencing patient's outcome. This study evaluated the interaction of two main cytokines in immune response after major trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma level of these cytokines is determined by mRNA expression of these cytokines genes which may decide the outcome of polytrauma patients.</p><p><b>METHODS</b>This prospective multicenter trial held at four trauma centers enrolled 54 polytrauma patients [Injury Severity Score (ISS) ≥ 16]. Plasma levels and mRNA expression of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was conducted to observe whether patients endured multiple organ dysfunction syndrome (MODS) and death. MODS evaluation was performed using sequential organ failure assessment (SOFA). Trauma load which in this study is represented with ISS, plasma level, expression of cytokine genes and patient's outcome were examined with correlation test and statistical analysis.</p><p><b>RESULTS</b>The elevated IL-6/IL-10 ratio indicated increased activity of systemic inflammation response, especially pro-inflammation response which bears higher probability of progressing to MODS and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30) showed that compensatory anti-inflammation response syndrome (CARS) state was more dominant than systemic inflammatory response syndrome (SIRS), indicating that malfunction and failure of immune system eventually lead to MODS and deaths. The statistical significance in plasma level of cytokines was found in the outcome group which was defined as bearing a low trauma load but mortality.</p><p><b>CONCLUSION</b>The pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome.</p>

Interleukin-22 promotes Th17 cells differentiation through up-regulating IL-6 production by rheuma-toid arthritis synovial fibroblasts / 中华微生物学和免疫学杂志

Objective To investigate the effects of interleukine-22 ( IL-22 ) on the expression of interleukin-6 (IL-6) by rheumatoid arthritis synovial fibroblasts (RASF), and to analyze their association with IL-17+CD4+T (Th17) cells differentiation.Methods RASF were isolated from six patients with rheu-matoid arthritis ( RA) and cultured in vitro.The expression of IL-6 at mRNA and protein levels by RASF were detected by qRT-PCR analysis and ELISA after treatment with different concentrations of IL -22 for dif-ferent periods of time.Anti-IL-22R1 blocking antibody and inhibitor assay were used to analyze the specific receptor and its downstream signaling pathways associated with IL-6 production.IL-22 pre-treated RASF and CD4+T cells were co-cultured for 3 days in the presence or absence of anti-IL-22R1 or anti-IL-6 to measure the percentage of Th 17 cells by flow cytometry .Results The expression of IL-6 by RASF was increased up-on IL-22 stimulation in a dose and time dependent manner (P<0.05), and that was closely related to IL-22R1 and its downstream signaling pathways of p38 and JAK2 (P<0.05).Co-culturing CD4+T cells with RASF and Transwell system indicated that the percentage of Th 17 cells was increased in IL-22 pre-treated group as compared with that in IL-22 untreated group , but it could be down-regulated by either blocking IL-22R1 or IL-6.Conclusion IL-22 promoted the expression of IL-6 by RASF and further enhanced Th 17 dif-ferentiation.Neutralizing IL-22 in synovium of patients with RA might be an effective therapeutic strategy for RA treatment.

Effect of fluoxetine and pyrrolidine dithiocarbamate on the lipopolysaccharide-induced interleukin 6 release in cultured rat astrocytes / 中华行为医学与脑科学杂志

Objective To investigate the effects of fluoxetine and pyrrolidine dithidarbamate (PDTC) on the lipopolysaccharide(LPS)-induced interleukine-6(IL-6) release in cultured rat astrocytes.Methods The purified astrocytes were cultured in 48-well tissue culture plate and classified into control group,LPS group,fiuoxetine group and PDTC group.Control group and LPS group were cultured as usual,and fluoxetine group and PDTC group were cultured with fluoxetine or PDTC at different concentrations for 48 hours,and then LPS group,Fluoxetine group and PDTC group were incubated with 1 ug/ml LPS for 24 hours.Finally,the levels of IL-6 in the cell supernatant were detected by enzymatic linked immunosorbent assay (ELISA) method.Results The level of IL-6 in LPS group ((1975.46 ± 171.54) pg/ml) was significantly higher than that in control group((10633 ± 782.15)pg/ml) (P ＜ 0.01).The levels of IL-6 were (6198.6 ± 379.4) pg/ml,(4973.6 ± 132.5) pg/ml and (4747.9 ±473.9) pg/ml respectively when the concentrations of fluoxetine were 10 μM,20 μM and 40 μM,and (4821.6 ±180.8) pg/ml,(4735.7 ±620.0)pg/ml and (3525.9 ± 240.0)pg/ml respectively when the concentrations of PDTC were 100 μM,150 μM and 200 μM.There was significant difference in the levels of IL-6 between LPS group and fluoxetine group (P ＜ 0.05),as well as between LPS group and fluoxetine group (P ＜ 0.05).Conclusion LPS can induce IL-6 release from astrocytes,while fluoxetine or PDTC at some concentrations can suppress LPS-induced IL-6 release.

Comparison of the neuroendocrine and inflammatory responses after laparoscopic and abdominal hysterectomy / 대한마취과학회지

BACKGROUND: Laparoscopic surgery is associated with a more favorable clinical outcome than that of conventional open surgery. This might be related to the magnitude of the tissue trauma. The aim of the present study was to examine the differences of the neuroendocrine and inflammatory responses between the two surgical techniques. METHODS: Twenty-four patients with no major medical disease were randomly assigned to undergo laparoscopic (n = 13) or abdominal hysterectomy (n = 11). Venous blood samples were collected and we measured the levels of interleukin-6 (IL-6), CRP and cortisol at the time before and after skin incision, at the end of peritoneum closure and at 1 h and 24 h after operation. RESULTS: The laparoscopic hysterectomy group demonstrated less of an inflammatory response in terms of the serum IL-6 and CRP responses than did the abdominal hysterectomy group, and the laparoscopic hysterectomy group had a shorter hospital stay (P < 0.05). The peak serum IL-6 (P < 0.05) and CRP concentrations were significantly less increased in the laparoscopic group as compared with that of the abdominal hysterectomy group (P < 0.05), while the serum cortisol concentration showed a similar time course and changes and there were no significant difference between the groups. The response of interleukin-6 showed a significant correlation with the response of CRP (r = 0.796; P < 0.05). CONCLUSIONS: The laparoscopic surgical procedure leaves the endocrine metabolic response largely unaltered as compared with that of open abdominal hysterectomy, but it reduces the inflammatory response as measured by the IL-6 and CRP levels.

Promotion of IL-6 gene transcription by panaxatriol saponin / 中国药理学通报

The RNA dot hybridization with human IL-6 cDNA showed that panaxatriol saponin (PTS) enhanced the interleukine-6(IL-6) mRNA concentration within PHA activated peripheral blood mononuclear cell (PBMC) byabout 4 folds,suggesting that PTS could promote the IL-6 gene transcription of lymphoid tissue