Placental tissue interleukin-10 receptor distribution in pre-eclampsia

PROBLEM: Reduced placental (trophoblast) cytokine interleukin-10 (IL-10) occurs in human pre-eclampsia. Along with an increase in inflammatory cytokines this may play an important role in the development of hypertension in pregnancy. It is not clear whether the changes in placental IL-10 are due to a change in the placental cell production of IL-10 or a result of changes in cytokine receptor status in adjacent tissues. This study is aimed at qualifying the presence and distribution of IL-10 receptors in women with a pre-eclamptic outcome compared to normal pregnancy and gestational hypertension. METHOD OF STUDY: Patients at the KGV Hospital, Sydney was selected for the study. Placentas were collected fresh and paraffin serial sections made. Sections were stained with IL-10 receptor antibody (10 microgram/mL) using avidin-biotin immunohistochemistry. Tissues of patients with pre-eclampsia (n=11) were compared with normal pregnancy (n=12). Pre-eclampsia was defined as a blood pressure >140/90 mmHg on two occasions and de nova proteinuria >300 mg per day which resolved post-partum. The fetal weights, gestational ages and maternal ages at delivery were compared (ANOVA) and the differences in staining of decidual and villous tissues were graded according to density. Statistical comparisons were made using the Kruskal-Wallis test. RESULTS: The groups were similar for maternal gestational age but delivered at earlier gestation and with lower fetal weight. There was significantly less villous cytotrophoblast staining for IL-10 receptor in all groups (P=0.012) compared to decidual trophoblast cells. There was equal intensity and density of extravillous straining observed in normal pregnancy (45 +/- 12%) positive cells compared to pre-eclampsia (27 +/- 12%). CONCLUSION: IL-10 receptors are present in greater concentration in the extravillous (decidual) trophoblast compared to villi. The decrease in IL-10 produced by trophoblast cells in pre-eclampsia is not explained by a difference in the IL-10 receptor distribution compared to normal pregnancy.     

Maternal Circulating TNF-α Levels are Highly Correlated with IL-10 Levels, but not IL-6 and IL-8 Levels, in Women with Pre-Eclampsia

Problem  Several lines of evidence have shown that maternal cytokine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-10 were altered in women with pre-eclampsia (PE) compared to those from normal pregnancies. In this study, we determined whether these cytokine levels are correlated before and after delivery in patients with PE.
Method of study  Venous blood was obtained from 50 women diagnosed with severe PE at the time of admission and 24 hr after delivery. Plasma concentrations for TNF-α, IL-6, IL-8, and IL-10 were measured by ELISA.
Results  There were no statistical differences for maternal levels of TNF-α, IL-6, IL-8, and IL-10 before and 24 hr postpartum. TNF-α and IL-10, but not IL-6 and IL-8, levels were significantly correlated before and 24 hr after delivery: TNF-α: y  = 19.963 + 0.953* x ; r ² = 0.924; IL-10: y  = 10.521 + 1.113* x ; r ² = 0.984, P  < 0.001, respectively. Furthermore, TNF-α levels were correlated with IL-10 levels, but not with IL-6 and IL-8 levels.
Conclusion  The correlation patterns of TNF-α with IL-10 and TNF-α with IL-6 and IL-8 suggest disparity in functional regulations between these cytokines in maternal circulation in PE.     

Increase in the production of interleukin-6, interleukin-10, and interleukin-12 by lipopolysaccharide-stimulated peritoneal macrophages from women with endometriosis

PROBLEM: To verify whether the peritoneal macrophage (PM) is activated in endometriosis. METHOD OF STUDY: We examined the synthesis of nitric oxide (NO), total antioxidant, interleukin (IL)-6, IL-10, and IL-12 by cultured PMs, which were either unstimulated or stimulated with lipopolysaccharide (LPS), from women with endometriosis (early, n = 12; advanced, n = 11) or without endometriosis (n = 13). RESULTS: After stimulation with 2 ng/mL LPS for 24 hr, PMs from women with early-stage endometriosis secreted more NO, IL-6, and IL-10 than the controls. Higher IL-12 levels were noted in women with advanced endometriosis when compared with the controls. After 2 ng/mL-LPS stimulation for 24 hr, we also detected higher total antioxidant levels in the advanced-endometriosis group than those in the early-endometriosis group. CONCLUSION: The increased production of IL-6, IL-10, and IL-12 by stimulated PMs confirmed previous observations that the PM is the principle source of these cytokines in peritoneal fluid.     

Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines

BACKGROUND: Decreased exposure to microbial stimuli has been proposed to be involved in the increased prevalence of atopic disease. Such a relationship was indicated by enhanced presence of typical probiotic bacteria in the intestinal flora correlating with reduced prevalence of atopic disease. Recent clinical trials suggested that probiotic bacteria may decrease and prevent allergic symptoms, but which (different) species or strains may contribute is poorly understood. OBJECTIVE: We sought to select probiotic bacteria by their ability to modulate in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs), to make a rational choice from available strains. METHODS: PBMCs, purified monocytes, and lymphocytes from healthy donors were co-cultured with 13 different strains of probiotic bacteria. The effect of lactic acid bacteria (LAB) on different cell populations and effects on cytokine production induced by the polyclonal T cell stimulator phytohaemagglutinin (PHA) was evaluated by measuring T helper type 1, T helper type 2 (Th2), and regulatory cell cytokines in culture supernatants by multiplex assay. RESULTS: PBMCs cultured with different strains produced large amounts of IL-10 and low levels of IL-12p70, IL-5, and IL-13. In PHA-stimulated PBMC cultures, the tested strains decreased the production of Th2 cytokines. Neutralizing IL-10 production resulted in partial to full restoration of Th2 cytokine production and concurred with an increase in pro-inflammatory cytokines such as IL-12p70 and TNF-alpha. Within the PBMCs, the CD14(+) cell fraction was the main source of IL-10 production upon interaction with LAB. CONCLUSION: Our results indicate that certain strains of lactobacilli and bifidobacteria modulate the production of cytokines by monocytes and lymphocytes, and may divert the immune system in a regulatory or tolerant mode. These specific strains may be favorable to use in prevention or treatment of atopic disease.     

Association of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in Iranian patients with pre-eclampsia

PROBLEM: Considering that certain cytokines may change during pre-eclampsia (PE), because of functional polymorphisms in their genes, our purpose was to determine the association between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) gene polymorphisms and development of PE. METHOD OF STUDY: The genetic polymorphisms of TNF-alpha and IL-10 was studied by polymerase chain reaction-sequence specific primers in the DNA of peripheral blood cell from 160 patients with PE and 100 healthy pregnant women. RESULTS: We found a significant difference between TNF-alpha A allele (-308) and G allele (-238) in PE patients compared with those of the control groups. A significantly higher C/C genotype frequency of IL-10 (-592 and -819) was observed in the PE patients than in the control groups. In addition, the frequencies of three common IL-10 haplotypes (GCC, ACC, and ATA) did not show any significant difference between the study groups. CONCLUSION: These findings would support the concept of contribution of TNF-alpha and IL-10 gene polymorphisms in the pathogenesis of PE in our population.     

人IL-10基因的克隆表达及表达产物活性的初步鉴定

目的:构建含人IL-10全基因序列的原核表达载体,并进行表达及产物活性的鉴定。方法:利用RT-PCR方法,从人肝癌细胞系HepG2的总RNA中扩增IL-10的全长编码序列。编码序列经测序验证后,将其克隆入表达载体PET-28 a( ),构建IL-10基因的重组原核表达载体。在大肠杆菌中诱导表达目的蛋白,表达产物采用Western blot和ELISA进行鉴定。结果:表达产物主要位于包涵体内。经Western blot分析和ELISA检测显示,表达产物的相对分子质量(Mr)同预期的结果相符,有结合抗体活性。结论:成功地扩增人IL-10全基因序列,并构建了含该基因序列的原核表达载体,在大肠杆菌中高效表达的表达产物具有抗原活性,为下一步制备抗IL-10的单克隆抗体(mAb)提供了必要的前提。     

Leptin, IL-10 and inflammatory markers (TNF-alpha, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women

PROBLEM: Despite progress in immunobiology, pre-eclampsia (PE) remains one of the most common reasons for women to die during pregnancy. The widespread pathophysiological mechanisms are endothelial dysfunction, oxidative stress and inflammation. The aim of this study was to assess the alteration in the levels of leptin, interleukin (IL)-10 and inflammatory cytokines [tumour necrosis factor (TNF)-alpha, IL-6 & IL-8] in pre-eclamptic (severe and mild), healthy pregnant and non-pregnant women and correlate these parameters with disease severity. METHOD OF STUDY: The levels of leptin, IL-10 and inflammatory cytokines were measured by high sensitivity enzyme-linked immunoabsorbant assay. The study subjects were 54 pre-eclamptic women (ten severe and 45 milder), compared by age matched 50 healthy pregnant and 27 non-pregnant women. Kruskal-Wallis non-parametric analyses of variance followed by Mann-Whitney U-test were used for statistical analysis. RESULTS: The levels of leptin, TNF-alpha, IL-6 & IL-8 in pre-eclamptic subjects were increased significantly when compared with the healthy control pregnant and non-pregnant (P < 0.000). The concentration of IL-10 has shown different pattern as its level decreased significantly (0.001) in pre-eclamptic women (overall) in comparison with control subjects (pregnant & non-pregnant). A combination of 80% or higher sensitivity and specificity was seen in the parameters analysed, except IL-8 and IL-10. CONCLUSION: Our findings suggest a relationship among TNF-alpha, IL-6, IL-8, IL-10 and leptin and indicate that altered levels of above markers in PE might be used as markers of pro-inflammation/anti-inflammation and endothelial dysfunction in pre-eclamptic pregnancies. These results also advocate the abnormal leptin and cytokine responses in mother, which might be involved in the pathogenesis of PE.     

Allergen-specific T cells from birch-pollen-allergic patients and healthy controls differ in T helper 2 cytokine and in interleukin-10 production

BACKGROUND: T helper (Th)2 cells play an important role in the development of IgE-mediated diseases, with local overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic inflammation. Furthermore, IL-10 has been suggested to play a modulatory role in the induction and maintenance of allergen-specific tolerance in human atopic diseases. AIM: We studied whether circulating allergen-specific Th2 cells persist outside the season of exposure in patients mono-sensitized to birch pollen and whether healthy control individuals also have allergen-specific Th2 cells. We also studied whether IL-10-producing allergen-specific T cells can be found in circulation either in healthy controls or in allergic patients. METHODS: Blood was drawn outside the birch-pollen season from 15 birch-pollen-allergic patients, with seasonal respiratory symptoms and with (n=12) or without (n=3) oral allergy syndrome, and from 10 matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with recombinant Bet v 1 allergen, control antigen tetanus toxoid (TT) and anti-CD3/CD80. In part of the cultures, rIL-4 was added in order to reinforce the allergen-specific Th2 cell responses. RESULTS: In the presence of rBet v 1, T cells from allergic patients, but not from healthy controls, produced IL-4, IL-5 and IL-13. IL-5 production by patients' T cells was further enhanced by adding more IL-4. In contrast, rBet v 1 together with IL-4-induced significant IL-10 production in control subjects but not in patients. Both Th1 and Th2 cytokines were equally induced by polyclonal stimulation in allergic patients and controls, but in the presence of IL-4, polyclonally induced IL-10 production was lower in the patient group. CONCLUSION: rBet v 1-specific Th2 cells circulate outside the season of exposure in the blood of birch-pollen-allergic subjects but not in healthy controls. Allergen-specific T cells were also demonstrated in controls but these cells produce IL-10 when stimulated with rBet v 1 in the presence of IL-4. Our data reveal a different allergen-induced cytokine profile in birch-pollen-allergic patients vs. controls, and suggest that a regulatory mechanism involving IL-4-induced allergen-specific IL-10 production might be defective in allergic subjects.     

Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia

Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (−1082 G/A; −592 A/C and −819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 −819 C allele (P = 0·003) and −592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to −1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: −1082A with −819C (P = 0·0016); −1082G with −819C (P = 0·0018); −819C with −592C (P = 0·001); −1082A with −592C (P = 0·032); and −1082G with −592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia.     

The mycotoxins citrinin and gliotoxin differentially affect production of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6, and the anti-inflammatory cytokine interleukin-10

BACKGROUND: Microbial growth is considered one of the major causes of indoor air problems. Moulds have been associated with asthma, allergy and a wide range of diffuse indoor air-related symptoms. However, mechanisms of the adverse health effects are not well understood. OBJECTIVE: We hypothesized that the mycotoxins citrinin and gliotoxin could cause an imbalance between the secretion of the pro-inflammatory cytokines TNF-alpha and IL-6 and the anti-inflammatory cytokine IL-10. METHODS: We investigated the influence of citrinin and gliotoxin on the human monocytic cell line Mono-Mac-6 (MM6) with and without lipopolysaccharide -stimulation. The levels of IL-10, IL-6 and TNF-alpha were analysed in cell culture supernatants by ELISA. Cell viability and cell apoptosis were measured by flow cytometry. RESULTS: The strongest inhibition of cytokine secretion was found for IL-10. IL-6 levels were found to decrease in a dose-dependent manner along with reduced cell viability. TNF-alpha levels increased with low gliotoxin exposure (less than 100 ng/mL), but decreased significantly at 375 ng/mL and higher along with increased cell apoptosis and reduced cell viability. TNF-alpha levels were not reduced by citrinin exposure. CONCLUSION: We observed a cytokine imbalance with a more pronounced reduction of IL-10 concentrations compared with those of TNF-alpha and IL-6. We suggest that low exposure doses of citrinin and gliotoxin (corresponding to less than 100 ng/mL gliotoxin and less than 10 mug/mL citrinin) may inhibit IL-10 and lead to increased risk of an inflammatory response with relative overproduction of TNF-alpha and IL-6. The findings and their clinical implications must be verified by human studies. However, we speculate that the observed biological effects may be of importance as they may partly explain the occurrence of diffuse general indoor air-related symptoms as well as the worsening of asthmatic inflammatory reactions experienced in mouldy environments.     

Immunological similarities between implantation and pre-eclampsia

PROBLEM: Cytokines are involved in implantation success and failure. We envisage that they could be similarly involved in pre-eclampsia (PE). MATERIALS AND METHODS: First, we review the primipaternity and primiparity concepts and then why natural killer (NK) cells are involved in implantation. We stress that the common event in all PE is vascular remodelling. RESULTS AND CONCLUSION: We conclude that PE could involve cytokine and/or NK dysfunctions, and propose a working hypothesis.     

Strategies for use of IL-10 or its antagonists in human disease

Summary: Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen-presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T-helper 1 (Th1)-type and Th2-type responses. This review discusses the potential use of IL-10 or agents that induce IL-10 as potential anti-inflammatory therapies in inflammatory diseases. Although IL-10-deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti-inflammatory properties of IL-10, although it should be noted that as discussed below, IL-10 can also promote B-cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL-10 may result in chronic infection. Thus, antagonists of IL-10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL-10, which may lead to potential uses of IL-10 or its antagonists in human disease.     

Maternal cytokine production patterns in women with pre-eclampsia

PROBLEM: To determine the levels of cytokines produced upon mitogenic or antigenic stimulation of maternal peripheral blood mononuclear cells (PBMC) from women with pre-eclampsia. METHOD OF STUDY: PBMC from 54 women with a history of successful pregnancy and 32 women undergoing pre-eclamptic delivery were stimulated with a mitogen or with autologous placental cells or with trophoblast antigens, and the levels of cytokines released into the culture supernatants then assessed by enzyme-linked immunosorbent assay. RESULTS: Significantly higher levels of the Th1 cytokines, interferon-gamma, and tumor necrosis factor-alpha were produced by the pre-eclamptic group than by the normal pregnancy group, which on the contrary showed significantly greater production of the Th2 cytokines, interleukin (IL)-4, IL-5, IL-6 and IL-10. A comparison of the ratios of Th2 to Th1 cytokines indicates a higher Th1 cytokine bias in pre-eclampsia as compared with normal pregnancy. CONCLUSIONS: These data are suggestive of a maternal pro-inflammatory cytokine bias in pre-eclampsia.     

Aberrant uterine natural killer (NK)-cell expression and altered placental and serum levels of the NK-cell promoting cytokine interleukin-12 in pre-eclampsia

PROBLEM: Natural killer (NK) cells are the most abundant lymphocyte population at the maternal-fetal interface. They are suggested to be important during placentation by controlling trophoblast invasion. If placentation is suboptimal, pre-eclampsia can occur. METHOD OF STUDY: Decidual NK (dNK) cells were examined at delivery in 46 women, 22 pre-eclamptic women and 24 healthy controls, by staining for CD56 and CD94 with immunohistochemistry (IHC). Furthermore, we investigated the placental expression and the serum levels of the NK-cell activating cytokines interleukin(IL)-12, IL-15, IL-18 and the anti-inflammatory cytokine IL-10 by IHC and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Pre-eclamptic women had higher number of CD56+ and CD94+ cells in the decidua, indicating an altered receptor expression of dNK cells. We also demonstrate for the first time that the villous trophoblasts show strong immunostaining for IL-12 in placentae from healthy controls, while women suffering from pre-eclampsia have significantly less IL-12. However, pre-eclamptic women had significantly elevated IL-12 and IL-15 levels in serum. CONCLUSION: Results show increased numbers and altered phenotype of dNK cells in pre-eclampsia, supporting the importance of these cells for a healthy pregnancy. The altered receptor expression of dNK cells together with diminished placental IL-12 expression could implicate an altered NK cell-regulation in pre-eclampsia.     

支气管哮喘患者血清IL-10、IL-5和ECP的变化及其意义

目的 通过对支气管哮喘患者和正常对照组的血清IL-10, IL-5和 ECP水平的测定以及相互关系的研究,探讨它们在支气管发病中的作用.方法 应用Pharmacia UniCAP系统和ELISA方法分别测定支气管哮喘患者和正常对照组的血清E CP和IL-10、IL-5水平.结果 正常对照组和发作期的支气管哮喘患者的 ECP水平分别为(3.97±2.13) μg/L和(21.76±12.08) μg/L.正常对照组,支气管哮喘ECP 升高组和支气管哮喘ECP正常组的血清IL-5水平分别为(10.90±4.41) pg/mL,(20.62± 15.7 4) pg/mL和(9.24±7.16) pg/mL.正常对照组和支气管哮喘ECP升高组之间IL-5水平有显著差异(P＜0.01),正常对照组和支气管哮喘ECP正常组之间IL-5水平无差异(P＞0.05) ,支气管哮喘ECP正常组和ECP升高组之间IL-5水平有显著差异(P＜0.01),ECP与IL-5 明显相关 ,两者之间的相关系数r=0.465(P＜0.01).正常对照组,支气管哮喘ECP升高组和支气管哮喘ECP正常组的血清IL-10水平分别为(38.28±15.17) pg/mL,(22.76±15.25) pg/mL 和(42.32±14.61) pg/mL,支气管哮喘ECP正常组和ECP升高组之间IL-10水平有显著差异( P＜0. 01).结论 支气管哮喘的发生与嗜酸粒细胞有密切的关系,ECP和IL-5可反映嗜酸粒细胞的活化程度,在支气管哮喘发作时嗜酸粒细胞处于激活状态,易于释放蛋白颗粒;IL-5对嗜酸粒细胞有调控作用.支气管哮喘组的血清IL-10水平较正常对照组低,提示支气管哮喘患者IL-10分泌减少,不能有效抑制炎症或促炎症细胞因子的合成及释放,亦即不能有效抑制炎症反应,可能是导致或加重气道炎症的原因之一.     

Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase

Eicosanoids (prostaglandins and leukotrienes) are important mediators of inflammatory responses. These lipid mediators may also regulate the production of peptide mediators of the immune system. In this study, we investigated the effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on interleukin (IL)-10 production. IL-10 is a key regulator of immune and inflammatory responses, and previous studies have suggested that prostaglandins effect their immunosuppressive functions in part by stimulation of IL-10 production. We therefore investigated whether leukotriene production would have a similar role in regulation of IL-10 production. We have made the striking observation that absence of 5-LO-derived leukotrienes results in increased IL-10 production with a concomitant decrease in the production of pro-inflammatory cytokines, including tumour necrosis factor (TNF)-alpha and IL-12. Moreover, T-cell cytokine production in the absence of 5-LO-derived leukotrienes results in increased IL-4 production and decreased interferon (IFN)-gamma production. This may be in part secondary to increased IL-10 production and its effects on dendritic cell function resulting in altered T-cell differentiation. These findings indicate that, in addition to the central role leukotrienes play in the acute inflammatory response, endogenous leukotrienes are also important regulators of inflammatory cytokine production, via regulation of IL-10 production and in vivo differentiation of T cells.     

Evolutionary adaptations to pre-eclampsia/eclampsia in humans: low fecundability rate, loss of oestrus, prohibitions of incest and systematic polyandry

Gestational-hypertension/pre-eclampsia occurs in approximately 10% of human pregnancies. This persistent complication of pregnancy has been reported to occur more frequently in couples conceiving very shortly after the beginning of their sexual relationship and/or after a change in paternity. Primipaternity may be the leading cause of pre-eclampsia in women under 30 years of age when genetic susceptibility to cardio-vascular disease has not yet been expressed, especially in women before their twenties, who for the last 40,000 years have perhaps comprised the age group when the majority of parturients classified as Homo sapiens sapiens initiated their reproductive life. In terms of evolution, the prevalence of pre-eclampsia represents a distinct reproductive disadvantage in humans as compared with other mammals. Indeed, pre-eclampsia is a consequence of the defect of the normal human-specific deep endovascular invasion of the trophoblast. The large size of the human fetal brain imposing this deep trophoblastic invasion induced the need for major immunogenetic compromises in terms of paternal-maternal tissue tolerance. The price that mankind has had to pay to adapt to the pre-eclampsia risk is a low fecundability rate and therefore loss of oestrus, possibly a step in the deviation between apes and hominids. Further, pre-eclampsia risk may be a contributing factor leading to the rejection of systematic polyandry in human societies and have influenced prohibition of incest.     

Role of Endothelin and Inflammatory Cytokines in Pre‐eclampsia – A Pilot North Indian Study

Citation Sharma D, Singh A, Trivedi SS, Bhattacharjee J. Role of endothelin and inflammatory cytokines in pre‐eclampsia – a pilot north Indian study. Am J Reprod Immunol 2011; 65: 428–432 Problem Pre‐eclampsia is new onset hypertension during pregnancy with proteinuria. The initiating event in pre‐eclampsia is postulated to involve reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium. Cytokines also appear to contribute to the development of the pathological condition. The aim of this study was to evaluate the role of cytokines in pre‐eclampsia and to study the relationship between endothelin‐1 and cytokines with the severity of the disease. Method of study This cross‐sectional study included 300 women with pre‐eclampsia and 200 healthy pregnant women. Their blood samples were analyzed for endothelin‐1 and inflammatory cytokines. Results Increased endothelin‐1 and cytokines [tumor necrosis factor‐α, interleukin‐2 (IL‐2) and γ‐interferon (IFN‐γ)] levels were found in pre‐eclampsia (P < 0.001). Significant positive correlation was seen between endothelin‐1 and cytokine level (IL‐2 and IFNγ) in the pre‐eclamptic group (P = 0.001). Conclusion We conclude that pre‐eclampsia is associated with increased levels of both endothelin‐1 and circulating inflammatory cytokines, which points toward the role of endothelial and inflammatory components.     

Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery

The prognostic significance of IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery was investigated. To this end, 50 candidate patients with colon cancer for surgery were admitted to the study. Of these, 30 could be subjected to a potentially curative surgery. Cytokine serum levels at several time points before and after surgery were measured by ELISA. Circulating levels of IL-10 and IL-6 were found to be elevated in cancer patients with respect to controls. Both IL-10 and IL-6 serum levels were demonstrated to predict the likelihood of curative surgery (predictive accuracy, 83.3%). IL-10 serum levels returned to normal in all but 6 patients who underwent curative surgery. These latter had tumor recurrence (predictive accuracy, 100%). In contrast, IL-6 serum levels significantly decreased in all patients, regardless of whether cure was surgically achieved, but did not normalize. On multivariate analysis, basal IL-10 serum levels were found to be among the variables significantly predicting the disease-free survival rate. Stepwise regression selected tumor stage, basal IL-10 serum level, and basal CEA serum level as the best combination of variables for prediction of the likelihood of tumor recurrence. In conclusion, preoperative serum levels of IL-10 were shown to be useful markers for predicting both likelihood to perform curative surgery and, in combination with the 16th postoperative day IL-10 serum levels, tumor recurrence (predictive accuracy, 73.6 and 96%, respectively). IL-6 serum levels were found to have a more limited prognostic role.