Interleukin-6 Genotypes Research Articles

Immune Mechanisms in Non–Hodgkin Lymphoma: Joint Effects of the TNF G308A and IL10 T3575A Polymorphisms with Non–Hodgkin Lymphoma Risk Factors

Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A, rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors for non-Hodgkin lymphoma (NHL) in a large pooled analysis. We systematically investigated the effects of other established NHL risk factors in relation to the tumor necrosis factor (TNF) G308A or interleukin 10 (IL10) T3575A genotypes. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) from 1,172 cases and 982 population-based controls in a U.S. multicenter study. We investigated NHL overall and two common subtypes [diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma]. NHL risks were increased among those with both an autoimmune condition and the TNF G308A GA/AA (OR(NHL), 2.1; 95% CI, 1.0-4.2) or the IL10 T3575A TA/AA genotype (OR(NHL), 1.6; 95% CI, 0.9-2.6) compared with individuals without an autoimmune condition and with the common TNF G308A GG or IL10 T3575A TT genotype, respectively; results were similar for DLBCL and follicular lymphoma. We found that elevated DLBCL risk associated with last-born status was more pronounced among those with TNF G308A GA/AA (OR(DLBCL), 2.7; 95% CI, 1.1-6.4) or IL10 T3575A TA/AA (OR(DLBCL), 2.9; 95% CI, 1.6-5.2). Similarly, elevated DLBCL risk associated with obesity (body mass index, > or = 35 versus <25 kg/m(2)) was observed only among those with TNF G308A GA/AA (OR(DLBCL), 2.5; 95% CI, 1.1-5.7) or IL10 T3575A TA/AA genotypes (OR(DLBCL), 2.0; 95% CI, 1.1-3.5). These exploratory results require replication but provide evidence that autoimmune conditions, late birth order, and obesity act partly through a common inflammatory pathway, posing a greater risk to individuals with variant TNF and IL10 genotypes than those with wild-type alleles.

Serum level and genotype of interleukin-6 in patients with esophageal cancer

To investigate the polymorphism of the interleukin-6 (IL-6) gene promoter-572C/G and -634C/G in patients with esophageal cancer, and to study the relation between the serum level and genotype of interleukin-6 and esophageal cancer. Peripheral blood samples were collected from 118 patients with esophageal cancer and 130 healthy persons as controls. The polymorphism of IL-6 was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The serum level of IL-6 was determined by enzyme-linked immunosorbent assay (ELISA). The frequency of the genotype GG of the IL-6 (-634) site in the cancer group was 12.7%, significantly higher that that of the control group (3.8%, P<0.05). The risk of esophageal cancer of the G allele carriers was 1.759 times that of the C allele carriers (OR=1.759, 95% CI=1.150-2.691). The serum level of IL-6 of the esophageal cancer group was (16.9+/-5.3) ng/L, significantly higher than that of the control group [(4.6+/-2.6) ng/L, P<0.01]. The serum level of IL-6 of the esophageal cancer with the G allele carriers was (18.8+/-6.1) ng/L, significantly higher than that of the esophageal cancer without the G allele carriers [(13.2+/-6.0) ng/L, P<0.01]. There was no significant difference in the distribution of the IL-6 gene-572C/G polymorphism between the 2 groups (P>0.05). IL-6 gene-634C/G polymorphism is associated with the esophageal cancer. The IL-6 allele G carriers may be at increased risk of the esophageal cancer because of the increase of the IL-6 expression.

Proximal interleukin‐10 gene polymorphisms in Italian patients with systemic sclerosis

Interleukin-10 (IL-10) can favour the development of fibrosis by promoting a relative shift towards T helper 2 responses. Three single base pair substitutions in the 5' flanking region of the IL-10 gene (G/A -1082, C/T -819 and C/A -592) influence the amount of IL-10 secreted in cell cultures: the GCC haplotype is associated with an increased production, while the ACC and the ATA haplotypes are associated with intermediate and decreased production. Accordingly, three phenotypes have been individuated: high producers (GCC+/GCC+), medium producers (GCC+/GCC-) and low producers (GCC-/GCC-). We hypothesised that IL-10 haplotypes and genotypes are differently expressed in patients with systemic sclerosis (SSc) with the limited cutaneous SSc (lcSSc) subset or the diffuse cutaneous SSc (dcSSc) subset. One hundred and sixty-one unrelated Italian patients with SSc and 94 controls have been included. Their DNA was extracted and stored before being analysed by polymerase chain reaction with sequence-specific primers. The GCC haplotype is overrepresented in patients with SSc; subjects with dcSSc were the primary contributors to these results (dcSSc: 52.2% vs controls: 37.2%; chi2= 8.519, 2 d.f., corrected P= 0.04). In Scl70-positive patients, the GCC haplotype increased the likelihood of presenting the dcSSc subset [chi2= 12.56, P < 0.0005; odds ratio (OR) = 3.89, 95% confidence interval (CI(95)) = 1.69-9.08]; these results were confirmed at the phenotypic level (chi2= 11.67, 2 d.f., P= 0.003). In Scl70-positive patients, the high-producing phenotype was associated with poor survival, independently from disease subset and gender (hazard ratio = 9.9, CI(95)= 1.6-61.27, P < 0.05). The IL-10 haplotype and genotype associated with high IL-10 production may alter the susceptibility to SSc and/or its expression, increasing the prognostic value of other well-known markers of disease severity.

The IL6 −174G/C polymorphism and sudden infant death syndrome

The interleukin-6 genotype (IL6 -174GG) has been proposed to be associated with sudden infant death syndrome (SIDS). The aim of this study was to investigate the -174G/C polymorphism in 175 Norwegian SIDS cases and 71 controls. There were no differences in genotype distribution between these two groups (p = 1.0). This confirms the findings in a combined SIDS group compared with European Caucasian controls, but not findings in smaller cohorts of SIDS cases from Australia and England. The discrepancy may result from bias introduced when investigating only a few SIDS cases, differences in diagnostic criteria when diagnosing the cause of death as SIDS, and differences in the distribution of the -174G/C polymorphism in different ethnic groups. Findings of an activated immune system in SIDS indicate that genes involved in the immune response are of importance. However, because there are several polymorphisms in the IL6 gene promoter that could potentially regulate the expression of the gene, more than one polymorphism should be investigated to assess the involvement of the IL-6 gene in SIDS.

The association of the composite IL‐1 genotype with periodontitis progression and/or treatment outcomes: a systematic review

Genetically transmitted traits such as cytokine gene polymorphisms may accentuate the host inflammatory response to the bacterial challenge and influence susceptibility to periodontitis. To systematically review the evidence of an association between the interleukin-1 (IL-1) composite genotype, i.e. presence of the allele 2 in the gene clusters IL-1A-889 and in IL-1B +3953, and periodontitis progression and/or treatment outcomes. Based on the focused question, a search was conducted for longitudinal clinical trials comparing progression of periodontitis and/or treatment outcomes in IL-1 genotype-positive (carrying allele 2) and IL-1 genotype-negative (not carrying allele 2) subjects. A search in the National Library of Medicine computerized bibliographic database MEDLINE and a manual search were performed. Selection of publications, extraction of data and validity assessment were made independently by two reviewers. The search provided 122 titles of which 11 longitudinal publications were included. The heterogeneity of the data prevented the performance of a meta-analysis. While findings from some publications rejected a possible role of IL-1 composite genotype on progression of periodontitis after various therapies, other reported a prognostic value for disease progression of the positive IL-1 genotype status. When assessed on a multivariate risk assessment model, several publications concluded that the assessment of the IL-1 composite genotype in conjunction with other covariates (e.g. smoking and presence of specific bacteria) may provide additional information on disease progression. The small sample size of the available publications, however, requires caution in the interpretation of the results. Based on these findings, (i) there is insufficient evidence to establish if a positive IL-1 genotype status contributes to progression of periodontitis and/or treatment outcomes. Therefore, (ii) results obtained with commercially available tests should be interpreted with caution.

Ethnic differences in interleukin 6 (IL‐6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels

Preterm birth (PTB) is a significant neonatal health problem that is more common in African-Americans (AA) than in European-Americans (EA). Part of this disparity is likely to result from the differing genetic architectures of EA and AA. To begin assessing the role of these differences, patterns of genetic variation in two previously proposed candidate genes, encoding interleukin 6 (IL6) and its receptor (IL6R), were analyzed in mothers and fetuses from 496 EA birth-events (149 cases and 347 controls) and 397 birth-events in AA (76 cases and 321 controls). IL-6 levels in amniotic fluid (AF) samples were determined in a subset of these pregnancies. Case-control comparisons revealed a single SNP in IL6R associated with PTB (p=0.04 for allelic and p=0.05 for genotype association). In addition, all of the SNPs studied showed significant frequency differences between AA and EA in at least one comparison, significantly in excess of that expected from general population databases. Higher IL-6 concentrations were associated with the IL6 SNP -661 in EA preterm samples (p=0.0056), and this result seems to be driven by microbial invasion of the amniotic cavity, indicating a gene by infection interaction. These findings indicate that, as a function of IL6 genotype, EA and AA women respond differently to infection with respect to their expression of IL-6. Our data support differential genetic control of levels of IL-6 in amniotic fluid between EA and AA.

Medical Contraindications to Implant Therapy: Part II: Relative Contraindications

Systemic conditions and habits influence dental implant survival to varying degrees. Illnesses that impair the normal healing cascade worsen surgical success. The mere presence of a disease, however, does not necessarily preclude implant therapy or affect significantly long-term outcomes. Certain disorders, when controlled, or other situations allow implant survival rates that match those in health. This paper reviews these relative contraindications, which include adolescence, aging, osteoporosis, smoking, diabetes, positive interleukin-1 genotype, human immunodeficiency virus positivity, cardiovascular disease, and hypothyroidism.

The interleukin-10 gene promoter polymorphism −1087AG does not correlate with clinical outcome in non-Hodgkin's lymphoma

The Interleukin 10 (IL-10) gene is highly polymorphic, and the IL-10(-1087AG) (rs1800896) gene variation is the only so far studied intensively in association with certain diseases. Conflicting data have been published about an association of IL-10(-1087AG) gene variation with lower rates of complete remission and lower overall survival (OS) in patients with diffuse large B-cell lymphoma. To further investigate this in malignant lymphoma, we established the IL-10 genotypes in patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's Lymphoma Study Group. In our study, allele frequencies of lymphoma patients are comparable as in healthy controls. No increase of IL-10(-1087G) alleles was found. In addition we did not find any difference in OS or event-free survival between patients with IL-10(-1087AA) and the other genotypes. Comparable results were obtained for the IL-10 loci at -3538 (A/T), -1354 (A/G), -824 (C/T) and -597 (A/C) (rs1800890, rs1800893, rs1800871 and rs1800872).

Interleukin 10 Regulates Inflammatory Cytokine Synthesis to Protect Against Lipopolysaccharide-Induced Abortion and Fetal Growth Restriction in Mice1

Interleukin 10 (IL10) is a potent immune-regulating cytokine and inhibitor of inflammatory cytokine synthesis. To evaluate the anti-inflammatory role of IL10 in pregnancy, the response of genetically IL10-deficient mice to low-dose lipopolysaccharide (LPS)-induced abortion was examined. When IL10-null mutant C57Bl/6 (Il10(-/-)) and control (Il10(+/+)) mice were administered low-dose LPS on Day 9.5 of gestation, IL10 deficiency predisposed to fetal loss accompanied by growth restriction in remaining viable fetuses, with an approximately 10-fold reduction in the threshold dose for 100% abortion. After LPS administration, inflammatory cytokines tumor necrosis factor-alpha (TNFA) and IL6 were markedly increased in serum, uterine, and conceptus tissues in Il10(-/-) mice compared with Il10(+/+) mice, with elevated local synthesis of Tnfa and Il6 mRNAs in the gestational tissues. IL1A and IL12p40 were similarly elevated in serum and gestational tissues, whereas interferon gamma (IFNG) and soluble TNFRII content were unchanged in the absence of IL10. Recombinant IL10 rescued the increased susceptibility to LPS-induced fetal loss in Il10(-/-) mice but did not improve outcomes in Il10(+/+) mice. IL10 genotype also influenced the responsiveness of mice to a TNFA antagonist, etanercept. Fetal loss in Il10(-/-) mice was partly alleviated by moderate or high doses of etanercept, whereas Il10(+/+) mice were refractory to high-dose etanercept, consistent with attenuation by IL10 status of TNFA bioavailability after etanercept treatment. These data show that IL10 modulates resistance to inflammatory stimuli by downregulating expression of proinflammatory cytokines TNFA, IL6, IL1A, and IL12, acting to protect against inflammation-induced pathology in the implantation site.

Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients

Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) coinfection poses a difficult therapeutic problem. Response to HCV-specific therapy is variable but might be influenced by host genetic factors, including polymorphisms of cytokine genes. Here, we studied whether interleukin-6 (IL-6) C174G gene polymorphism affects the response to antiviral treatment in HCV-infected HIV-positive subjects. We determined IL-6 genotypes in HIV-positive patients with acute (n = 52) and chronic (n = 60) hepatitis C treated with pegylated interferon-alpha. Two hundred ten HCV monoinfected, 197 HIV monoinfected, and 100 healthy individuals were studied as controls. Patients were classified into high and low producers according to IL-6 genotypes. Rates of sustained virological responses (SVRs) were compared between the IL-6 genotypes. Signal transducer and activator of transcription three phosphorylation was analyzed by Western blot in HCV core-transfected human hepatoma cell line (HUH7) cells. Distribution of IL-6 genotypes did not differ significantly between the study groups. SVR was achieved in 63% of HIV/HCV coinfected patients. Carriers of the IL-6 high producer (HP) genotype had significantly higher SVR rates than patients with an IL-6 low producer genotype (70.1% versus 52%; P < 0.002). This effect was seen in both HIV-positive patients with acute (74% versus 33%; P < 0.05) and chronic (66% versus 33%; P < 0.05) hepatitis C. Multivariate analysis confirmed IL-6 HP carriage as an independent positive predictor for SVR (Odd's ratio 6.1; P = 0.004). This effect corresponds to the in vitro observation that in HCV core-transfected HUH7 cells, IL-6 overcomes the HCV core-mediated inhibition of STAT3 activation. Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation.

High-sensitivity C-reactive protein concentration in patients with myocardial infarction-environmental factors, and polymorphisms in interleukin-10 and CD14 genes

It has been shown that high-sensitivity C-reactive protein (hsCRP) concentrations are associated with elevated risk of myocardial infarction, but the mechanisms regulating hsCRP concentration are not completely elucidated yet. In our study, association of interleukin-10 (IL-10) and CD14 polymorphisms and environmental factors with the risk of myocardial infarction was studied. The study group consisted of 284 male patients aged below 65 years, admitted to hospital for myocardial infarction. The controls were age-matched individuals selected from a 1% representative population sample of adult men. While there was no difference in body mass index (BMI), the patients more frequently had abdominal-type obesity. hsCRP concentration was higher in patients (2.12+/-2.31 mg/L) than in controls (1.40+/-1.56 mg/L; p=0.001), in spite of statin treatment in most of the patients. No significant difference in lipoprotein concentrations was found. There was no difference in IL-10 and CD14 genotype distributions between the patients and controls. In smoking patients carrying the CD14 C allele, hsCRP concentration was significantly higher (p=0.0012) than in a non-smoking patients with the same allele. According to linear regression analysis, statin treatment was the only variable with an influence that reached statistical significance in the patient group, while in the control group, age, smoking, education and BMI significantly influenced hsCRP concentration. There was no association between IL-10 and CD14 polymorphisms and myocardial infarction occurrence. Gene-environment interaction may play an important role in influencing hsCRP concentration.

Interleukin-10 [ATA] promoter haplotype and prostate cancer risk: A population-based study

Interleukin-10 (IL-10) is a multifunctional cytokine acting as inhibitor of inflammatory and immune responses as well as tumour induced angiogenesis. A common [ATA] haplotype formed by polymorphisms at positions −1082, −819 and −592 in the promoter of the IL-10 gene is a strong determinant for IL-10 expression. The presence of this haplotype can be determined by analysis of the −592C > A polymorphism. To analyse the role of the IL-10 [ATA] haplotype in prostate cancer we performed a case-control study including 561 prostate cancer patients and 561 male, age-matched, control subjects without malignant disease. The IL-10 −592C > A polymorphism was determined by a 5′-nuclease assay (TaqMan). IL-10 −592 CC, CA and AA genotype frequencies were not significantly different between patients (53.6%, 40.0%, 6.4%) and controls (54.3%, 39.6%, 6.1%; p = 0.96). IL-10 genotypes were furthermore not associated with tumour characteristics such as histological grade, T stage, PSA levels at diagnosis, or age at diagnosis. Therefore we conclude that the IL-10 −592C > A promoter polymorphism, tagging the IL-10 low-producer [ATA] haplotype, is not associated with risk for prostate cancer.

The Potential Prognostic Value of Some Periodontal Factors for Tooth Loss: A Retrospective Multilevel Analysis on Periodontal Patients Treated and Maintained Over 10 Years

The great challenge in clinical periodontology is assigning a prognosis to a periodontally affected patient. Many different factors can affect the long-term maintenance of periodontally compromised teeth. The main questions usually considered by the periodontist are: 1) Will a tooth lose more bone in the future? 2) Will the tooth itself be lost in the future? The purpose of this retrospective study was to evaluate the value of some clinical, genetic, and radiographic variables in predicting tooth loss in periodontal patients (aged 40 to 60 years) treated and maintained for 10 years. Sixty consecutive non-smoking patients (aged 46.77 +/- 4.96 years) with moderate to severe chronic periodontitis (CP) were treated with scaling and root planing (SRP). Some patients also underwent additional surgical treatments. All patients were maintained in the same private practice for 10 years. The frequency of recall appointments was 3.4 +/- 1.0 months. At baseline (T(0)) and 10 years later (T(2)) the following clinical variables were evaluated: the number of teeth, probing depths (PD), tooth mobility (TM), and presence of prosthetic restorations (PR). In addition, radiographic measurements were taken of the mesial and distal distances from the cemento-enamel junction (CEJ) to the bottom of the defect (BD), to the bone crest (BC), and to the root apex (RA). At T(2), a genetic test to determine the IL-1 genotype and genetic susceptibility for severe periodontal disease was performed for all 60 patients, and they were classified as IL-1 genotype positive (G+) or negative (G-) according to the test results. Tooth loss was used as the outcome variable. Different predictor variables were then tested using a two-level statistical model (patient and tooth levels). At the patient level, these were: age, gender, mean bone loss (mean CEJ-BD)(T0), the interleukin-1 (IL-1) genotype, the interaction between mean bone loss, and IL-1 genotype (mean CEJ-BD(T0) x IL-1 genotype). At the tooth level, the variables were: TM(T0), prosthetic restorations (PR)(T0), molar teeth (MT)(T0), the infrabony component of the defect (BC-BD)(T0), PD(T0), bone level (CEJ-BD)(T0), and residual supporting bone (BD-RA)(T0). Among the considered predictor variables, the following were significantly associated with the outcome variable: 1) MT(T0) (P <0.0001); 2) BC-BD(T0) (P = 0.0377); and 3) BD-RA(T0) (P <0.0001). MT(T0) were found to be more prone to loss and the amount of BD-RA(T0) prognostic for tooth loss: the lower the residual amount of supporting bone, the higher the probability of tooth loss. Conversely, the BC-BD(T0)was associated with a reduced probability of future tooth loss: the greater the infrabony component, the lower the probability of tooth loss. None of the other considered predictors proved predictive for tooth loss. Within the scope of this study, many traditional prognostic factors were ineffective in predicting future tooth loss and, therefore, were of no prognostic value. Conversely, a few specific factors at the tooth level emerged as viable prognostic factors. The use of these factors may be of great value to practitioners as predictors of tooth loss when assigning a prognosis.

Association of interleukin‐1 gene polymorphisms with gastric cancer: A meta‐analysis

Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the risk of the original studies. Thirty-nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta-analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL-1B-511T, -31C, +3954T and IL-1RN*2 was 1.26 (95% confidence interval (CI): 1.03-1.55), 1.00 (95% CI: 0.82-1.22), 1.37 (95% CI: 0.94-2.00) and 1.20 (95% CI: 1.01-1.41), respectively. A stratified analysis showed that IL-1B-511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12-2.57). Moreover, IL-1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09-1.54). In conclusion, IL-1B-511 and IL-1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer.

Interleukin‐6 Gene Polymorphism −174G/C Influences Plasma Lipid Levels in Women

Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) have been associated with cardiovascular risk factors. The objective of this study was to investigate potential associations between the promoter polymorphism IL-6 -174G/C and the following indices of metabolism: BMI, waist-to-hip ratio, and plasma levels of IL-6, cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, leptin, and C-reactive protein in 252 42-year-old women and 245 51-year-old men. Subgroups were also studied 5 years later. The CC genotype of the IL-6 polymorphism was associated with lower levels of cholesterol and low-density lipoprotein (p < 0.001) in women. This finding was replicated in the follow-up, when a significant association between the CC genotype and low triglycerides was also observed. The association between the C allele and lipid pattern found in women was not found in men, where on the contrary, C carriers tended to display elevated triglycerides. IL-6 genotype was not associated with IL-6 plasma levels in either sample. The results suggest different effects of the IL-6 polymorphism on metabolic indices in women and men. None of the associations between IL-6 genotype and lipid pattern seemed to result from an effect of the polymorphism on IL-6 plasma levels.

Interleukin-10 and its role in clinical immunoparalysis following pediatric cardiac surgery*

A systemic insult is associated with subsequent hyporesponsiveness to endotoxin (as measured by ex vivo tumor necrosis factor [TNF]-alpha production) and an increased risk of late nosocomial infection in some patients. When combined with low monocyte surface major histocompatibility complex class II expression, this state of altered host defense is now commonly referred to as immunoparalysis. This study was undertaken to delineate the relationship between observed levels of the anti-inflammatory cytokine interleukin-10, common genetic polymorphisms that influence these levels, and the occurrence and severity of endotoxin hyporesponsiveness in children following elective cardiac surgery requiring cardiopulmonary bypass. A prospective observational clinical study. A tertiary pediatric cardiac center. Thirty-six infants and children <2 yrs of age undergoing elective cardiac surgery requiring cardiopulmonary bypass. None. We investigated the production of TNF-alpha, interleukin-6, interleukin-8, interleukin-1 receptor antagonist, and interleukin-10 in whole blood in response to lipopolysaccharide (Neisseria meningitides 10 ng/mL) in samples drawn before, during, and up to 48 hrs after surgery. Patients were genotyped for the -1082, -819, and -592 interleukin-10 promoter polymorphisms. Whole blood cytokine response to lipopolysaccharide was reduced postoperatively to </=50% of preoperative levels for all cytokines measured. Stimulated cytokine production was lowest in cases with the highest postoperative plasma interleukin-10 levels, which were in turn associated with the GCC haplotype. Those patients in whom the whole blood response to endotoxin was maintained (TNF-alpha >100 pg/mL) over the first 48 hrs were more likely to have an uncomplicated short stay (odds ratio 4.7, 95% confidence interval 1-22). Immediately following cardiac surgery, many children become relatively refractory to lipopolysaccharide stimulation. This immunoparalysis appears to be related in part to high circulating levels of interleukin-10 and places these patients at increased risk of postoperative complications. Interleukin-10 genotype may be a risk factor for immunoparalysis.

The association of −627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus

The objective of the study is to examine whether interleukin-10 (IL-10) promoter polymorphism is a marker of susceptibility of systemic lupus erythematosus (SLE) in Chinese patients in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Each polymorphism was detected as a result of a polymerase chain reaction (PCR)-based restriction analysis. The PCR product length was determined to be 412 bp (CC) whereas two fragments of 236 and 176 bp were determined to be excisable lengths (AA). The relationship between the IL-10 gene polymorphism and clinical manifestations of SLE was evaluated. For the genotype and allelic frequency, there were statistically significant differences between the SLE patients and the normal control subjects (p=0.007 and 0.003, respectively). But we did not detect any association of carriage rate of the IL-10 polymorphism and the normal control subjects (p=0.077). Furthermore, we did not detect any association of IL-10 genotype with antinuclear antibody, malar rash, photosensitivity, discoid lupus, mucosal ulcer, arthritis, serositis, hematology, immunology, involvement of central nervous system, and renal disease involvement in the SLE patients. The significant relation of -627 IL-10 genotype and allelic frequency with SLE implies that the IL-10 gene polymorphism can serve as a candidate gene marker for further study in patients with SLE in Taiwan.

MUltiplex Measurement of Cytokine/Receptor Gene Polymorphisms and interaction Between Interleukin-10 (-1082) Genotype and Chorioamnionitis in Extreme Preterm Delivery

To establish a multiplex amplification refractory mutation system (ARMS) in fluid and dried whole blood, and to perform a pilot study to examine the role for single-nucleotide polymorphisms (SNPs) of inflammation-associated genes (interleukin [IL]-1 and -10, tumor necrosis factor-alpha [TNFA], and toll-like receptor-4 [TLR4]) and their interaction with clinical chorioamnionitis (CAM) in prematurity. We established a quadruplex ARMS to detect the four above SNPs. Fifty-four women delivered at gestational age less than 32 weeks and 83 healthy female volunteers were genotyped. We compared (1) mothers of preterm infants with volunteers, and (2) women delivered before 29 weeks' gestation (n = 29) with those delivered at 29 to 31 completed weeks (n = 25). Multiplex ARMS is feasible using both fluid and dried whole blood. We found no overall differences in genotype and allele frequencies between mothers of preterm infants and volunteers. Among women who had a preterm delivery, those with both CAM and IL10(-1082)*G allele, the risk for delivery before 29 weeks was markedly increased (odds ratio [OR] 22, 95% confidence interval [CI] 2.5 - 191). The presence of both CAM and IL10(-1082)*G might play a role in extreme preterm delivery less than 29 weeks.

Interleukin-10 Polymorphisms, Cancer Susceptibility and Prognosis

Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic functions and may have both tumour-promoting and -inhibiting properties. A large number of polymorphisms (primarily single nucleotide polymorphisms (SNPs)) have been identified in the IL-10 gene promoter. Convincing evidence that certain of these polymorphisms are associated with differential expression of IL-10 in vitro and in some cases in vivo has been obtained and a number of studies have investigated associations between IL-10 polymorphisms and cancer susceptibility/prognosis. The results from 22 studies in 13 different malignancies are reviewed. In 17 of these studies, positive associations between IL-10 genotype or haplotype and disease susceptibility and/or progression were reported. In some of these cancers genotypes associated with low IL-10 expression were a risk factor for disease or disease progression, while in others genotypes associated with high IL-10 expression were a risk factor. Published findings in breast cancer are as yet conflicting. Most, but not all of the studies reviewed are based on small sample sizes and a limited number of IL-10 polymorphisms. However, the preliminary data obtained thus far indicate that larger studies are required in a number of cancers, in order to confirm initial results, extend studies to include more detailed genotype/haplotype analysis and combine genotype and gene expression studies in the same subjects. Such studies will contribute significantly to our understanding of the biological role of IL-10 in cancer development.

The interleukin-6 gene –174G>C and –572G>C promoter polymorphisms are related to cerebral aneurysms

Background and aims: An important part is played by inflammation in intracranial aneurysm formation. The hypothesis that there is an association of the proinflammatory cytokine interleukin-6 (IL-6) genotypes (−572G>C and...