Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese

Interferon gamma (IFN-gamma) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-gamma activates macrophages, while IL-10 downregulates the expression of T helper type 1 cytokines, MHC class II antigens and costimulatory molecules on macrophages. Associations of IFN-gamma -179 (G/T), +874 (A/T), +875 miscrosatellite CA repeats and +4766 (C/T), and IL-10 -1082 (A/G), -819 (C/T) and -592 (C/A) with tuberculosis (TB) were investigated in 385 HIV-negative patients and 451 controls in a Hong Kong Chinese population. The frequency of a low IFN-gamma-producing +874 A/A genotype was significantly over-represented in the patient group (P<0.001, OR=3.79, 95% CI=1.93-7.45). We identified 10 alleles in the IFN-gamma CA repeats and observed a significant difference in allele frequency distribution between patients and controls (P<0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (P<0.001, OR=4.56, 95% CI=2.21-9.43) as observed in +874 A/A genotype. Weak associations of the IL-10 GCC/- genotype (P=0.04) and the low IFN-gamma-producing A/A genotype (P=0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.     

IFN-γ与 IL-4基因多态性与儿童哮喘易感性及外周血IFN-γ、IL-4和IgE的关系

目的: 探讨IFN-γ和 IL-4 基因多态性与儿童哮喘易感性及血浆IFN-γ、IL-4和IgE的相关性。方法: 用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)法检测100例哮喘儿童和122例对照儿童IFN-γ基因-179G/T、 IL-4 基因-33C/T和-589C/T位点基因型;等位基因特异性-聚合酶链反应(AS-PCR)法检测IFN-γ基因+874A/T位点基因型;毛细管电泳法检测IFN-γ基因CA重复序列基因型;ELISA法测定血浆IFN-γ、IL-4和IgE。结果: 100例哮喘儿童和122例对照儿童IFN-γ基因-179位点均为GG纯合子,未检测到突变基因型。IFN-γ基因+874A/T位点和CA重复序列的基因型和等位基因频率分布在哮喘组和对照组间无显著差异(P>0.05);+874位点多态性与血浆IFN-γ水平相关,AA基因型IFN-γ含量低于AT基因型(P<0.05)。 IL-4 基因-33C/T和-589C/T位点的基因型和等位基因频率分布在哮喘组和对照组间有显著差异(P<0.05);-33和-589位点TT基因型外周血IL-4和总IgE浓度均高于CT基因型,只有-33位点与血浆IL-4水平存在相关性(P<0.05)。结论: IFN-γ基因+874A/T和CA重复序列多态性可能与儿童哮喘无相关性,+874A/T位点多态性与IFN-γ水平相关。 IL-4 基因-33TT和-589TT基因型可能为儿童哮喘的易感基因型,-33位点多态性与IL-4表达水平相关。     

Polymorphisms in the immunoregulatory genes are associated with hematopoietic recovery and increased susceptibility to bacterial infections in patients with thalassaemia major undergoing matched related hematopoietic stem cell transplantation

In this study, the impact of polymorphisms in the genes of proinflammatory (IL-β, TNF-α, IL-6, IFN-γ), anti-inflammatory (transforming growth factor [TGF]-β, IL-10, IL-Ra), and other immunoregulatory factors (FcγRIIa, NOS3) along with the conventional risk factors on the rate of hematopoietic recovery and first episodes of bacterial, viral, or invasive fungal infections in 102 patients with β-thalassaemia major who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with relatively uniform protocols at our center from June 1995 to June 2004 with a minimum follow-up of at least 2 years were studied retrospectively for 180 days after hematopoietic stem cell transplantation (HSCT). Our data show that (1) donor IL-1RN?2/2 (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.17-5.09; P = .018) and FCγRIIA +4481G/G genotypes (HR, 3.1; 95% CI, 1.56-6.31; P = .001) increased the incidence of bacterial infection; (2) fungal infection was increased in recipients with whose donors had IFN-γ +874T/T genotype (HR, 3.8; 95% CI, 1.08-13.62; P = .037); (3) time to neutrophil recovery was shorter in splenectomized patients (HR, 3.1; 95% CI, 1.70-5.64; P < .001), donors without IL-10 -1082A, -819T, and -592A haplotype (HR, 1.6; 95% CI, 1.02-2.39; P = .039), and recipients with IFN-γ +874A/A genotype (HR, 1.6; 95% CI, 1.05-2.56; P?= .029); and (4) time to platelet recovery was shorter in patients with IL-10 -1082A/A genotype (HR, 1.8; 95% CI, 1.14-2.68; P = .010) and with donors having TNF-α -308G/G genotypes (HR, 1.8; 95% CI, 1.06-2.93; P = .028). These data suggest that outcome after allogeneic stem cell transplantation could be affected by many factors. The mechanisms by which they bring about such impact needs further evaluation.     

Investigation on the association between inerleukin-10 -592C/A, 819C/T and -1082A/G gene polymorphisms and development of diabetic nephrophathy

We conducted a case-control study to investigate the association between interleukin (IL)-10-592C/A, -819C/T and -1082A/G polymorphisms and susceptibility to diabetic nephropathy. A hospital-based case-control study was taken in our study. A total of 172 patients with proven type 2 diabetes mellitus and 344 controls were recruited from the First Affiliated Hospital of Xinxiang Medical University between March 2012 and October 2014. Genotyping of IL-10 -592C/A, -819C/T and -1082A/G polymorphisms was done by done by PCR-RFLP methods. By the χ² test, the distributions of the GG, GA and AA genotypes in IL-10 -1082A/G were significantly different between patients with diabetic nephropathy and control subjects (χ² = 8.09, P = 0.02). By conditional logistic regression analysis, we found that the AA genotype of IL-10 -1082A/G was associated with an elevated risk of diabetic nephropathy compared to the GG genotype in codominant model, and the adjusted OR (95% CI) was 2.38 (1.23-4.57). In dominant model, the GA+AA genotype was associated with a significantly increased risk of diabetic nephropathy compared to the GG genotype in dominant model (OR = 1.47, 95% CI = 1.05-2.16). In recessive model, the AA genotype could influence the susceptibility to diabetic nephropathy when compared with the GG+GA in recessive model (OR = 2.08, 95% CI = 1.12-3.85). In conclusion, we suggested that IL-10 -1082A/G gene polymorphism was correlated with development of diabetic nephropathy, but no association was observed between IL-10 -819T/C and -592A/C and risk of diabetic nephropathy.     

-174G/C interleukin-6 gene polymorphism and the risk of transplanted kidney failure or graft loss during a 5-year follow-up period

The influence of cytokine gene polymorphisms on transplanted kidney outcome is not well understood. The aim of this one-centre study was to analyse the association between tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and transforming growth factor-β1 (TGF-β1) genotypes and the incidence of delayed graft function (DGF), acute rejection (AR) and 5-year kidney graft loss. Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence-specific primers for TNF-α (-308A/G), IL-10 (-1082A/G, -819T/C and -592A/C), IL-6 (-174G/C), IFN-γ (+874T/A) and TGF-β1 (in codons 10T/C and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5-year follow-up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF-β1 genotype. There was an association between -174G/C IL-6 gene polymorphism and the death-censored kidney graft survival. The risk of graft loss during 5-year follow-up period was greater by 57% for GG or GC (higher IL-6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen-DR mismatch. -174G/C IL-6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional expression.     

IL-10 high producing genotype predisposes HIV infected individuals to TB infection

Interleukin (IL-10), an anti-inflammatory cytokine, is known to have dual effect on the host immune system. One of these roles is that it provides an effective autoregulatory mechanism which protects the host from excessive inflammation and tissue damage which is in part initiated by the Th1 driven pro-inflammatory immune responses during infections (such as TB, HIV and malaria). However, though beneficial, this autoregulatory mechanism is at times exploited by pathogens which evade elimination by Th1 driven immune response leading to chronic infections. The main aim of this study therefore was to study the influence of IL-10 polymorphism in relation to its levels with respect to HIV-TB co-infection. A total of 452 participants were categorized into HIV (121), active tuberculosis (TB) (118), HIV-TB (HT) (106) groups and healthy control group (107). Polymorphism for IL-10 gene (positions -1082, -819, -592) was studied using ARMS-PCR, RFLP. IL-10 and IFN-γ levels in antigen stimulated cultures were measured using ELISA. Statistical analysis was performed using Chi-Square (χ(2)) test, One-way ANOVA and t-tests. IL-10 (-1082) GG genotype was positively associated with HIV-TB, whereas AG with HIV and AA with TB. The cohort with GG genotype also had significantly high stimulated levels of IL-10 compared to AG and AA. AC genotype was significantly frequent in HIV-TB group at IL-10 (-592) position when compared with controls. HIV positive individuals with GG genotype at IL-10 (-1082) position and high IL-10 levels may have a high risk of developing TB co-infection.     

Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load and susceptibility to human T-lymphotropic virus type 1 infection

Interleukin-18 (IL-18) and interferon-gamma (IFN-γ) exert important functions in both innate and adaptive immune responses against intracellular pathogens and viruses. Previous studies suggested that host genetic factors, including cytokines gene polymorphisms, could be involved in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Thus, we analyzed -137C/G and -607A/C of the IL-18 promoter and +874T/A of the IFN-γ in DNA samples from 98 HTLV-1-infected individuals exhibiting or not clinical symptoms and 150 healthy control individuals. The IL-18 promoter -607CC genotype was significantly lower in HTLV-1 asymptomatic carriers (HAC) and HTLV-1-infected individuals (HAC + HAM/TSP) than healthy control group. In contrast, the -607AC genotype was significantly higher in HAC and HTLV-1-infected individuals group compared to the healthy control group. The -137G/-607A IL-18 haplotype was higher in infected group than healthy control group, and the -137C/-607C IL-18 haplotype was increased in the healthy control group compared to the others. Finally, the IFN-γ polymorphism analysis showed that the HTLV-1-infected individuals with +874AT genotype presented higher proviral load than +874AA genotype. These data indicate that the IL-18-607AC genotype and -137G/-607A haplotype could be a risk factor for HTLV-1 infection, whereas the protective effect could be conferred by -607CC genotype and -137C/-607C haplotype. Also, the IFN-γ could be implicated on the proviral load levels.     

白介素10的基因多态性与尖锐湿疣的相关性研究

目的探讨白介素10（IL-10）基因启动子-1082位点基因多态性与尖锐湿疣的相关性。方法采用焦磷酸测序法（Pyrosequencing）检测30例尖锐湿疣患者（观察组）和50例健康体检者（对照组）IL-10基因启动子-1082G/A位点基因型和等位基因频率;同时采用双抗体夹心ELISA法测定对照组和观察组的血清IL-10水平。结果观察组血清IL-10水平显著高于对照组（P〈0.01）。观察组IL-10基因启动子-1082 G/A位点GG基因型分布频率和G等位基因频率高于对照组（P〈0.01）。在观察组中表达GG基因型患者的血清IL-10水平显著高于表达其它基因型患者的血清IL-10水平（P〈0.05）。结论 IL-10基因多态性与尖锐湿疣易感性可能相关,IL-10基因启动子-1082 G/A位点GG基因型携带者对尖锐湿疣的易感性高。     

Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients.     

The +874T/A polymorphism in the interferon-γ gene and tuberculosis risk: an update by meta-analysis

The +874T/A polymorphism in the interferon-γ (IFN-γ) gene has been extensively examined for association to tuberculosis (TB); however, results of different studies have been inconsistent. The aim of this study was to comprehensively analyze the genetic risk of the +874T/A polymorphism in IFN-γ gene for TB by meta-analysis. A total of 4553 cases and 4631 controls in 21 case-control studies were included in this meta-analysis. The results indicated that the variant T allele carriers had a 27% decreased risk of TB, when compared with the homozygote AA (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.61-0.87 for TT + TA versus AA). In the subgroup analysis by ethnicity, significant decreased risks were associated with T allele carriers in Asians (OR= 0.71, 95% CI = 0.52-0.97, p = 0.03) but not in Caucasians (OR = 0.87, 95% CI = 0.65-1.17, p = 0.37). Our results suggest that the IFN-γ +874T/A polymorphism contributes to susceptibility to TB.     

The combined effect of interleukin (IL)-10 and IL-12 polymorphisms on induced cytokine production

Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with an antagonistic effect of the T-helper (Th)1/Th2 cytokine balance and provide a functional link between innate and adaptive immune responses. The aim of the study was to investigate the combined effect of -1082A*G in IL10 and +16974A*C in IL12B single nucleotide polymorphisms (SNPs) on induced cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. The presence of the high-producer IL-12p40 genotype led to diminished production of IL-10 as determined by the -1082*G allele of SNP in IL10. Significantly decreased IL-10 production was detected in AA+AG/GG in comparison with the low-producer IL-12p40 (AC/CC+AG/GG) genotype combination after stimulation with C3bgp (2 +/- 4 vs. 29 +/- 14.2 pg/ml; p = 0.0003) and LPS (33.4 +/- 13.5 vs. 93.3 +/- 59.6 pg/ml; p = 0.019). IL-12p40 production was independent of IL10 genotype. The present results demonstrated that the production of IL-10 from PBMC depended on both -1082A*G in IL10 and +16974A*C in IL12B polymorphisms.     

Association between the Interleukin 10-1082G>A polymorphism and coronary heart disease risk in a Caucasian population: a meta-analysis

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and studies have shown the involvement of IL-10 in the atherosclerotic process. The IL-10-1082G/A polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with coronary heart disease (CHD) risks, but previous results have been conflicting. We performed a meta-analysis using six eligible case-control studies (including 14 data sets) with a total of 5006 patients and 3968 controls to summarize the existing data on the association between the IL-10-1082G/A polymorphism and CHD risk. Compared with the common IL-10-1082G/A GG genotype, the carriers of variant genotypes (IL-10-1082GA/AA) had a 1.12-fold elevated risk of CHD (95% CI = 1.01-1.23, P = 0.03) under the dominant genetic model, as estimated using a random effect model. The effect of the IL-10-1082G/A polymorphism was further evaluated using stratification analysis. In the three disease of artery studies, with the variant genotypes had a not obvious increased risk of disease of artery (OR = 1.19, 95% CI = 0.98-1.44, P = 0.08) as estimated using a fixed effect model. Similar results were found in the nine myocardial infarction studies (OR = 1.13, 95% CI = 1.00-1.27, P = 0.05). It was also demonstrated that the increased risk of CHD associated with IL-10-1082G/A variant genotypes was more pronounced in Caucasians (OR = 1.12, 95% CI = 1.01-1.23, P = 0.03). Our meta-analysis suggests that the IL-10-1082G/A polymorphism genotypes (GA+AA) might be associated with an increased risk of CHD, especially in Caucasians.     

Suppressed type 1, type 2, and type 17 cytokine responses in active tuberculosis in children

Type 1 cytokine responses are known to play an important role in immunity to tuberculosis (TB) in children, although little is known about other factors that might be important. In addition, children are more prone to developing extrapulmonary manifestations of TB than adults. To identify the immune responses important both in control of infection and in extrapulmonary dissemination, we examined mycobacterium-specific cytokine responses of children with pulmonary TB (PTB) and extrapulmonary TB (ETB) and compared them with those of healthy control children (HC). No significant differences were found in the cytokine responses either with no stimulation or following mycobacterial-antigen (Ag) stimulation between children with PTB and ETB. On the other hand, children with active TB compared with HC showed markedly diminished production of type 1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), 2 (interleukin 4 [IL-4] and IL-13), and 17 (IL-17A, IL-21, and IL-23)-associated cytokines with no stimulation and in response to mycobacterial antigens. This was not associated with significantly altered production of IL-10 or transforming growth factor β (TGF-β). Among children with ETB, those with neurologic involvement exhibited more significantly diminished Ag-driven IFN-γ and IL-17 production. Pediatric TB is characterized by diminished type 1, 2, and 17 cytokine responses, with the most profound diminution favoring development of neurologic TB, suggesting a crucial role for these cytokines in protection against pediatric tuberculosis.     

Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population

We conducted a case-control study to investigate the association between IL-10 gene polymorphism (-1082A/G, -819T/C, and -592A/C) and risk of acute pancreatitis in a Chinese population. A total of 240 patients with proven acute pancreatitis and 240 control subjects were collected between May 2012 and January 2015. Genotyping of the IL-10-1082A/G, -819T/C, and -592A/C gene polymorphisms was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By univariate logistic regression analysis, patients with acute pancreatitis were more likely to have higher BMI (OR=2.12, 95% CI=1.45-3.12; P<0.001) and have a habit of alcohol drinking (OR=2.01, 95% CI=1.37-2.95; P<0.001). There were significant differences in the genotype distributions of IL-10-1082A/G between patients with acute pancreatitis and control subjects (χ²=9.97, P=0.007). By multiple logistic regression analysis, we found that individuals with the GG genotype of IL-10-1082A/G were associated with an increased risk of acute pancreatitis when compared with the AA genotype (OR=2.32, 95% CI=1.20-4.59; P=0.007). In dominant and recessive models, the IL-10-1082A/G gene polymorphism was significantly correlated with an elevated risk of acute pancreatitis, and the adjusted Ors (95% CI) were 1.50 (1.03-2.20) and 1.99 (1.06-3.79), respectively. However, no significant different was found between IL-10-819T/C and -592A/C gene polymorphisms and susceptibility to acute pancreatitis. In conclusion, we suggest that IL-10-1082A/G gene polymorphisms contribute to the development of acute pancreatitis in codominant, dominant and recessive models.     

Cytokine gene polymorphisms and breast cancer susceptibility and prognosis.

Single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes are associated with differential levels of cytokine expression. We hypothesized that these SNPs might influence breast tumour development and progression by affecting the efficiency of the antitumour immune response and/or pathways of angiogenesis. A total of 144 female breast cancer patients and 263 cancer-free population controls were genotyped for the interleukin (IL)-1beta-511 (T/C), IL-6 -174 (G/C), tumour necrosis factor (TNF)-alpha-308 (A/G), IL-10 -1082 (A/G), IL-8 -251 (A/T) and vascular endothelial growth factor (VEGF) -1154 (A/G) SNPs, using amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and TaqMan (Applied Biosystems, Foster City, CA, USA) 5' nuclease assays for allelic discrimination. No significant associations were seen. Patient-control comparisons revealed a non-significant trend for association between the TNF-alpha-308 GG genotype and breast cancer compared to controls (79.7 vs. 68.2%, P = 0.03, Pc = 0.54). Stratification of the patient group according to the Nottingham Prognostic Index and individual prognostic factors revealed trends for association between IL-6 -174 GC and IL-8 -251 AA genotypes and markers of poor prognosis (P = 0.04, Pc = 0.72 and P = 0.02, Pc = 0.36, respectively). There were also trends for associations between VEGF -1154 AG and IL-1beta-511 TC genotypes and markers of good prognosis (P = 0.02, Pc = 0.36 and P = 0.05, Pc = 0.90, respectively). These results suggest that the role of cytokine promoter SNPs in both susceptibility to and prognosis in breast cancer requires further investigation in a larger study.     

Cytokine gene polymorphism and Chlamydia trachomatis-specific immune responses

Chlamydia trachomatis-induced fallopian tube damage leading to tubal factor infertility (TFI) is linked with TNF, IL-10, and probably IFNG gene polymorphisms. The aim of this study was to clarify the contribution of these cytokine gene polymorphisms to interindividual variation in C trachomatis-specific immune responses and the cross-regulation of secreted cytokines and single nucleotide polymorphisms (SNPs). Cytokine polymorphisms (IL-10 -1082A/G, -819T/C, and -592A/C, IFNG +874T/A, and TNF -308G/A) were genotyped by polymerase chain reaction in 139 women. C trachomatis-specific immune responses were measured using lymphocyte proliferation (LP) induced by C trachomatis E and F strains and chlamydial heat shock protein 60 antigens. Cytokine secretion was measured in culture supernatants of infected and uninfected mononuclear leukocytes. IL-10 -1082/-819/-592 and IFNG +874 SNPs were associated with the intensity of LP responses to C trachomatis antigens. These cytokines also interact with each other and a cumulative effect of IL-10 -1082 and IFNG +874 genotypes was seen in LP responses to C trachomatis antigens. Our data suggest that interleukin-10 and interferon-γ regulate C trachomatis-specific immune responses in humans and that genetic variation in the expression of their coding genes explains interindividual variation in host immune responses to C trachomatis infection.     

Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment

During TB cytokines play a role in host defence. To determine the cytokine pattern during various disease stages of TB, serum levels of IL-12, interferon-gamma (IFN-γ), IL-4, IL-6 and IL-10 were measured in 81 patients with active TB, 15 patients during therapy and 26 patients after anti-tuberculous therapy as well as in 16 persons who had been in close contact with smear-positive TB and in 17 healthy controls. IFN-γ was elevated during active TB when compared with healthy controls, declining during and after treatment. IL-12 (p40 and p70) serum levels were not significantly higher in patients with active TB compared with any of the other groups. IL-4 levels were low in all groups. IL-6 and IL-10 serum levels were elevated in patients with active TB and during treatment. In patients with active TB serum levels of IFN-γ and IL-6 were higher in patients with fever, anorexia and malaise. IL-12 levels were higher in patients with a positive smear. Cytokine levels did not correlate with localization of TB (pulmonary versus extrapulmonary), or skin test positivity. Cytokines directing a Th1 response (IL-12) or a Th2 response (IL-4) were not elevated in sera of this large group of patients with pulmonary and extrapulmonary TB. In patients with active TB, cytokines that were elevated in serum were IFN-γ, IL-6 and IL-10.     

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (?1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (?1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25–9.45; p = 0.014) or 2.35 (1.05–5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.     

Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patients

Interleukin (IL)-10 is an important multifunctional cytokine with both anti-inflammatory and immunoregulatory effects in rheumatoid arthritis (RA). In the present study, we evaluated the frequency and potential impact of IL-10 promoter polymorphisms on susceptibility to and severity of RA in Polish in – patients with a high disease activity (mean DAS 28 C-reactive protein 5.25). DNA was obtained from 244 RA patients and 106 healthy controls. The −592C/A and −1082G/A IL-10 gene polymorphisms were amplified by polymerase chain reaction with restriction endonuclease mapping. The frequency of the IL-10-592CA, -592AA genotypes (respectively: 30% vs 5% and 7% vs 0%) and allele −592A (37% vs 5%) were significantly higher in RA patients as compared with a control group. We did not find any association of the IL-10-592C/A genotype distribution with disease parameters, except for an increased ESR (erythrocyte sedimentation rate) in patients with the −592CC genotype as compared with those with −592CA or −592AA genotypes (P = 0.01). The frequency of the IL-10-1082GG genotype was lower (P = 0.0001), and that of the IL-10-1082GA genotype was higher (P = 0.009) in RA patients comparing with the control group. In RA patients with −1082GA or −1082AA genotypes the time duration of the disease (P = 0.03), Health Assessment Questionnaire (HAQ) Score (P = 0.04) and PLT count (P = 0.001) were significantly increased as compared with subjects with −1082GG genotype. Presented findings indicate that IL-10-592C/A and IL-10-1082G/A polymorphisms may be considered genetic risk factors for RA susceptibility and severity.     

Single Nucleotide Polymorphisms in IL-10, IL-12p40, and IL-13 Genes and Susceptibility to Glioma

Glioma is one of the most aggressive and most common tumors of the central nervous system (CNS) in humans. The exact causes of glioma are not well known, but evidence suggests the involvement of genetic factors in addition to environmental risk factors. The present study aimed to determine whether polymorphisms in IL-10-1082A/G, IL-12p40 1188C/A, and IL-13+2044G/A (rs20541) are associated with the incidence of glioma in Iraqi patients. Ninety-six patients with different grades of glioma and 40 apparently healthy individuals were recruited. A blood sample and genomic DNA were collected from all subjects. The amplification refractory mutation system and sequence-specific primer polymerase chain reaction (PCR) were used for genotyping of IL-10-1082A/G and IL-12p40 1188C/A, respectively; whereas, the IL-13+2044G/A was detected by DNA sequencing after amplification of the genes by PCR.All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in patients and controls. In IL-10-1082A/G, these genotypes frequencies were AA (75%), AG (22.93%) and GG (2.07%) in patients as compared to similar frequencies (62.5%), (27.5%) and (10%) respectively, in controls. The variant IL-12p40 1188C/A genotype was AA (72.92%), AC (23.96%), and CC (3.13%%) in patients as compared to 65%, 30%, and 5%, respectively, in controls. The frequencies of IL-13+2044G/A genotypes (GG, GA, and AA) were 89.58%, 9.37%, and 1.04% among patients versus 47.5%, 32.5% and 20%, respectively, among controls. These results suggest a protective role of mutant alleles G and A in IL-10-1082A/G and IL-13+2044G/A against gliomas. Further studies with more rigorous parameter designs will be needed to confirm the current findings.