• IL-1 alpha polymorphism
• Indian
• periodontitis

• ALD
• IL1β
• TNF-α
• alcohol
• alcohol induced liver diseases
• liver microenvironment
• miRNA
• microRNA-124-3p

• Humans
• Chemokines/genetics
• Collagen/genetics
• Liver Cirrhosis/genetics
• Liver Diseases, Alcoholic/genetics
• Luciferases/genetics
• MicroRNAs/genetics
• Polymorphism, Single Nucleotide
• Transforming Growth Factor beta/genetics
• Tumor Necrosis Factor-alpha/genetics
• Interleukin-1beta/genetics

• (rs909253) +252 A/G SNP
• tumor necrosis factor beta (TNF‐β)
• type 2 diabetic
• urinary tract infection

Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians’ understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.

• Genotype
• Humans
• Immunologic Tests
• Inflammation
• Interleukin-10/genetics
• Interleukin-10/immunology
• Lichen Planus, Oral/genetics
• Lichen Planus, Oral/immunology
• Lupus Erythematosus, Discoid/genetics
• Lupus Erythematosus, Discoid/immunology
• Precancerous Conditions/genetics
• Precancerous Conditions/immunology
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/immunology

• National Natural Science Foundation of China

• Chronic Periodontitis
• Genetic Polymorphism
• Interleukin-10
• Interleukin-6
• Therapeutics

• meta
• periodontitis
• polymorphisms
• susceptibility
• tumor necrosis factor-alpha

• Asian People
• Case-Control Studies
• Genetic Predisposition to Disease
• Humans
• Observational Studies as Topic
• Periodontitis/genetics
• Polymorphism, Single Nucleotide
• Protective Factors
• Risk Factors
• Tumor Necrosis Factor-alpha/genetics

• co-administered drugs
• disease
• inter-subject variability
• monoclonal antibodies
• pharmacokinetics

• IL-10
• haplotype
• polymorphism
• primary open angle glaucoma

Obesity is associated with inflammation, which can disturb genome stability. Tumor necrosis factor (TNF-α) polymorphism was found to affect TNF-α protein production and inflammation. Therefore, the present study illustrates the relationship between TNF-α polymorphism, the degree of inflammation assessed by serum high sensitivity C-reactive protein concentration (CRP-hs) and basal DNA damage in patients with obesity (BMI 30–34.9 kg/m²) and control subjects with proper body mass (BMI < 25 kg/m²). A total of 115 participants (75 obese premenopausal women; and 40 age-, and gender-matched controls) were included. Biochemical parameters (serum concentrations of total-cholesterol, HDL-cholesterol, LDL- cholesterol, triglycerides, glucose, apolipoprotein AI, CRP-hs) and endogenous DNA damage (determined by comet assay) were measured. TNF-α G-308A polymorphism (rs1800629) was analyzed by PCR-RFLP (PCR-restriction fragments length polymorphism). An effect of TNF-α genotype on serum CRP-hs concentration was noted (p = 0.031). In general, carriers of the rare A allele of the TNF-α G-308A polymorphism had significantly lower endogenous DNA damage and serum CRP-hs concentrations than GG homozygotes, however, the protective effect of the A allele was especially visible in non-obese women. Serum CRP-hs concentrations and levels of DNA damage (% DNA in tail) were significantly higher in obese than in controls (p = 0.001 and p < 0.0001, respectively). The adjusted multiple linear regression analyses revealed a significant, independent impact of obesity on DNA damage (p = 0.00000) and no effect of other covariates i.e. age, TNF-α genotype and serum CRP-hs concentration. Our study showed that obesity has a significant impact on the levels of endogenous DNA damage. Obesity abolished the protective effect of A allele of the TNF-α G-308A polymorphism on DNA damage and on inflammation development observed in non-obese A allele carriers.

• CRP
• DNA damage
• Obesity
• Polymorphism
• TNF gene

• Chronic periodontitis
• Cytokine
• Diagnosis
• Gene
• Polymorphism

• Case-Control Studies
• Chronic Periodontitis/genetics
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Humans
• Polymorphism, Single Nucleotide

• Immunogenetic
• Liver

• association studies
• candidate gene
• genetic
• immunity
• oral ulcer
• polymorphisms

• Crohn’s disease
• IL-10
• IL-4
• Th2 cytokines
• genetics
• inflammatory bowel disease
• polymorphisms
• ulcerative colitis

Goose can develop severe hepatic steatosis without overt injury, thus it may serve as a unique model for uncovering how steatosis-related injury is prevented. To identify the markedly prosteatotic and protective mechanisms, we performed an integrated analysis of liver transcriptomes and gut microbial metagenomes using samples collected from overfed and normally-fed geese at different time points. The results indicated that the fatty liver transcriptome, initially featuring a ‘metabolism’ pathway, was later joined by ‘cell growth and death’ and ‘immune diseases’ pathways. Gut microbiota played a synergistic role in the liver response as microbial and hepatic genes affected by overfeeding shared multiple pathways. Remarkably, the complement system, an inflammatory component, was comprehensively suppressed in fatty liver, which was partially due to increased blood lactic acid from enriched Lactobacillus. Data from in vitro studies suggested that lactic acid suppressed TNFα via the HNF1α/C5 pathway. In conclusion, gut microbes and their hosts respond to excess energy influx as an organic whole, severe steatosis and related tolerance of goose liver may be partially attributable to gut microbiotic products and suppressed complement system, and lactic acid from gut microbiota participates in the suppression of hepatic TNFα/inflammation through the HNF1α/C5 pathway.

• Polymorphism; rheumatoid arthritis; tumor necrosis factor alpha

• Adiponectin receptor
• Fatty liver
• Goose
• Primary hepatocyte

• Serbian cohort
• genetic variant
• inflammatory bowel disease
• inflammatory gene
• predictive modeling

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. Various reports have implicated cytokine gene polymorphisms in susceptibility to develop some immune mediated conditions including OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk.

Forty two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms.

The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P<0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P>0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility.

It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease.

Tumor necrosis factor-alpha (TNF-α) contributes in inflammation and has been implicated in the development of colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in TNF-α promoter could affect the risk of CRC by regulating TNF-α production. This is the first study to investigate TNF-α SNPs in a Middle Eastern population. In this study, we examined three SNPs in TNF-α for association with CRC. One hundred CRC patients and 100 controls were genotyped for TNF-α -308, -238, and -857 using TaqMan allelic discrimination assay. The TNF-α -238 (G/A) genotype was significantly associated with high risk of CRC (p = 0.003552). The distribution of three genotypes of -238 G/A was significantly different between the controls and CRC patients even after Bonferroni’s correction. The AA genotype of -238 G/A SNP was observed at considerably higher proportion (13 %) in CRCs compared to controls (1 %). Additionally, similar to genotypes, the allelic frequencies of -238 G/A were significantly different between the CRC cases and controls (odds ratios (OR) = 7.647, χ² = 18.50, p = 0.00002). The genotype frequencies of -308 and -857 were not notably different between the cases and controls. TNF-α -238A may be useful as a screening marker to identify individuals prior to their acquiring CRC in the Saudi population although, further validations in larger cohorts are needed.

• Colorectal cancer
• Polymorphisms
• Tumor necrosis factor

• Interleukin-10 alleles in periodontitis
• interleukin-10 polymorphism
• interleukin-10 polymorphism in periodontitis
• promoter polymorphism in periodontitis
• single nucleotide polymorphism in periodontitis

Crohn’s disease (CD) is a chronic inflammatory disease in which cytokines play a pivotal role in the induction and maintenance of inflammation. Innate cytokine production is genetically determined and varies largely between individuals; this might impact the severity of inflammation. We aimed to assess whether ex-vivo endotoxin-stimulated levels of cytokines could be associated with disease phenotype.

Patients with quiescent CD (Harvey-Bradshaw Index ≤ 4 and negative inflammation markers) who were not using immunomodulating drugs or biologicals were eligible. Historical disease characteristics (localization, behavior, number of bowel resections, drug history, extra-intestinal symptoms) were extracted from medical records. We measured cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10) in supernatants of lipopolysaccharide (LPS) -stimulated whole blood cultures and correlated these with disease characteristics and age- and sex-matched healthy controls. In addition, we analyzed whether single nucleotide polymorphisms (SNPs) in the promoter region of the TNF-α gene were related to TNF-α levels.

We included 75 patients with CD and 24 healthy controls. Six patients were excluded because of increased inflammation markers resulting in a total of 69 patients. The mean age (SD) of patients with CD was 51.2 (12.3) years with a mean (SD) disease duration of 24.1 (11.5) years. Disease localization, peri-anal involvement and behavior were not related to LPS-stimulated TNF-α, IL-1β, IL-6 or IL-10 levels. In addition, combination of localization with behavior to differentiate mild from severe disease type showed no significant differences. TNF-α levels were higher in patients with CD (428 pg/ml IQR [267-468]) compared to healthy controls (459 pg/ml IQR [364-570], p=0.02). We found no associations between SNPs in the promoter region and TNF-α levels.

In this study, innate cytokine production of TNF-α, IL-1β, IL-6 and IL-10 was not related to historical disease characteristics or disease severity in patients with quiescent CD. These findings suggest that genetically determined levels of these cytokines obtained from LPS-stimulated whole blood cultures are not linked with disease behavior or severity.

• Case-Control Studies
• Crohn Disease/blood
• Crohn Disease/genetics
• Crohn Disease/immunology
• Crohn Disease/metabolism
• Cytokines/blood
• Cytokines/metabolism
• Female
• Humans
• Lipopolysaccharides/immunology
• Male
• Phenotype
• Polymorphism, Genetic
• Promoter Regions, Genetic
• Tumor Necrosis Factor-alpha/biosynthesis
• Tumor Necrosis Factor-alpha/genetics

• Polymorphisms
• Systemic lupus erythematosus
• TNF-α

• Expression
• Haplotype
• Interleukin-10
• Primary Sjögren’s syndrome
• mRNA
• sIL-10

Microglial cells are normally activated in response to brain injury or immunological stimuli to protect central nervous system (CNS). However, over-activation of microglia conversely amplifies the inflammatory effects and mediates cellular degeneration, leading to the death of neurons. Recently, cordycepin, an active component found in Cordyceps militarisa known as a rare Chinese caterpillar fungus, has been reported as an effective drug for treating inflammatory diseases and cancer via unclear mechanisms. In this study, we attempted to identify the anti-inflammatory role of cordycepin and its protective effects on the impairments of neural growth and development induced by microglial over-activation. The results indicate that cordycepin could attenuate the lipopolysaccharide (LPS)-induced microglial activation, evidenced by the dramatically reduced release of TNF-α and IL-1β, as well as the down-regulation of mRNA levels of iNOS and COX-2 after cordycepin treatment. Besides, cordycepin reversed the LPS-induced activation of NF-κB pathway, resulting in anti-inflammatory effects. Furthermore, by employing the conditioned medium (CM), we found cordycepin was able to recover the impairments of neural growth and development in the primary hippocampal neurons cultured in LPS-CM, including cell viability, growth cone extension, neurite sprouting and outgrowth as well as spinogenesis. This study expands our knowledge of the anti-inflammatory function of cordycepin and paves the way for the biomedical applications of cordycepin in the therapies of neural injuries.

• Animals
• Cell Death/drug effects
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Cells, Cultured
• Culture Media, Conditioned/pharmacology
• Deoxyadenosines/pharmacology
• Dose-Response Relationship, Drug
• Growth Cones/drug effects
• Growth Cones/metabolism
• Hippocampus/pathology
• Inflammation/pathology
• Lipopolysaccharides/pharmacology
• Mice
• Microglia/drug effects
• Microglia/metabolism
• NF-kappa B/metabolism
• Neurites/drug effects
• Neurites/metabolism
• Neurogenesis/drug effects
• Neurons/drug effects
• Neurons/pathology
• Neuroprotection/drug effects
• Signal Transduction/drug effects

• Interleukin-10
• Polymorphism
• Saudis
• Schizophrenia

• TNF-α
• meta-analysis
• periodontitis
• polymorphism
• susceptibility

• Crohn’s disease
• Inflammatory bowel disease
• Interleukin
• Interleukin receptor
• Polymorphisms
• Ulcerative colitis

• Colitis, Ulcerative/genetics
• Crohn Disease/genetics
• Gene Expression Regulation
• Genetic Markers
• Genetic Predisposition to Disease
• Genotype
• Humans
• Immune System
• Inflammatory Bowel Diseases/genetics
• Interleukins/genetics
• Phenotype
• Polymorphism, Genetic
• Receptors, Interleukin/genetics

• Genotypes
• Inflammation
• Pancreatic fibrosis
• Pancreatic stellate cells

• Alleles
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/pathology
• Crohn Disease/genetics
• Crohn Disease/pathology
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Interleukin-10/genetics
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic
• Risk Factors
• White People

• genetics
• inflammatory bowel disease
• single nucleotide polymorphisms
• tumor necrosis factor alfa

• Adolescent
• Adult
• Child
• Diabetes Mellitus, Type 1/genetics
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetics, Population
• Genotype
• Humans
• Lymphotoxin-alpha/genetics
• Male
• Polymorphism, Single Nucleotide
• Sex Factors
• Tunisia
• Young Adult

Most Crohn’s disease (CD) genes discovered in recent years are associated with biological systems critical to the development of this disease. TGFB1 and IL10 are cytokines with important roles in CD. The aim of this study was to evaluate the association between CD, its clinical features and TGFB1 and IL10 gene polymorphisms.

This case–control study enrolled 91 patients and 91 controls from the state of Bahia, Brazil. Five single nucleotide polymorphisms (SNPs) were studied in the TGFB1 gene (codon 10 T > C - rs1800470; codon 25 G > C - rs1800471) and IL10 gene (−1082 A > G - rs1800896; -819 T > C - rs1800871; -592 A > C - rs1800872). An analysis of the genetic polymorphisms was performed using a commercial kit. A comparison of allele frequencies and genotypes was estimated by calculating the odds ratio (OR) with a confidence interval adjusted via the Bonferroni test for a local alpha of 1%. A stratified analysis was applied for gender, race and smoking history. Patients with CD were characterized according to the Montreal classification.

The C allele and CC genotype of the TGFB1 gene rs1800470 were both significantly associated with CD. The stratified analysis showed no confounding factors for the co-variables of gender, race and smoking history. The IL10 gene rs1800896 G allele was significantly associated with age at diagnosis of CD, while the T allele of the IL10 gene rs1800871 was significantly associated with perianal disease. The SNPs rs1800871 and rs1800872 were in 100% linkage disequilibrium.

TGFB1 gene polymorphisms may be associated with susceptibility to the development of CD, and IL10 gene polymorphisms appear to influence the CD phenotype in this admixed population.

A polymorphic tetranucleotide (GAAT)_n microsatellite in the first intron of the canine tumor necrosis factor alpha (TNFA) gene was characterized in this study; 139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24 Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the presence of the 4 alleles (GAAT)₅, (GAAT)₆, (GAAT)₇ and (GAAT)₈, including 9 of the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic information content (PIC) value of this microsatellite locus varied from 0.389 to 0.749 and from 0.333 to 0.682, respectively, among the 6 breeds. The allelic frequency differed greatly among breeds, but this microsatellite marker was highly polymorphic and could be a useful marker for the canine TNFA gene.

Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) or ulcerative colitis are chronic intestinal disorders, which are on the increase in “Westernised” countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose of 8 μg/kg. However, to date, the results of the clinical trials have been disappointing. Although CD activity was reduced as measured by the CD activity index, IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10 supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.

• Inflammatory bowel disease
• Crohn’s disease
• Interleukin-10
• Recombinant human interleukin-10

• Crohn Disease/drug therapy
• Crohn Disease/physiopathology
• Dose-Response Relationship, Drug
• Humans
• Interleukin-10/physiology
• Interleukin-10/therapeutic use
• Recombinant Proteins/therapeutic use
• Treatment Outcome

The aim of this study was to investigate whether genetic variations at positions -1082, -819, and -592 in the interleukin (IL)-10 promoter affect IL-10 production in children with irritable bowel syndrome (IBS).

Ninety-four children with IBS and 102 children as healthy controls (HCs) were enrolled. Genomic DNA was extracted, and IL-10 -1082, -819, and -592 polymorphisms were detected by direct sequencing from all participants. Peripheral blood mononuclear cells (PBMCs) from 46 IBS children and 38 HCs were isolated and cultured with and without 5 ng/mL Escherichia coli lipopolysaccharide (LPS). IL-10 levels in the culture supernatants were measured by enzyme-linked immunosorbent assay.

There were no significant differences in the distribution of IL-10 -1082, -819, and -592 polymorphisms or in the allele and haplotype frequencies between IBS children and HCs. PBMCs from children with IBS had significantly lower IL-10 levels after LPS stimulation than PBMCs from HCs (p=0.011); however, LPS-induced IL-10 levels in PBMCs with different genotypes of -819 and -592 polymorphisms were not significantly different between IBS patients and HCs.

Although significantly lower LPS-induced IL-10 production by PBMCs was noted, it is unlikely that IL-10 production was fully genetically determined in our IBS children. ClinicalTrials.gov identifier: NCT01131442.

• Child
• Interleukin-10
• Interleukin-10 gene polymorphisms
• Irritable bowel syndrome

AIM: To explore the association between interleukin-10 (IL-10) 819T/C polymorphism and Crohn's disease susceptibility.

METHODS: A systematic search of electronic databases such as CBM, CNKI, PubMed, Elsevier and EMbase was performed to retrieve relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated using the RevMan 5.1.4 software, and publication bias was tested by Egger's regression test and Begg's test.

RESULTS: A total of 11 studies involving 1670 patients with Crohn's disease and 3312 healthy controls were identified. The results of meta-analyses showed no significant association between IL-10 819T/C polymorphism and susceptibility to Crohn's disease (for T/T vs C/C: OR = 0.90, 95% CI: 0.70 to 1.17; T/C vs C/C: OR = 0.84, 95% CI: 0.56 to 1.27; for dominant inheritance model: OR = 0.97, 95% CI 0.86 to 1.10; for recessive inheritance model: OR = 0.90, 95% CI: 0.71 to 1.14).

CONCLUSION: Current evidence strongly suggests that there is no significant association between IL-10 819T/C polymorphism and susceptibility to Crohn's disease.

• Crohn's disease
• Interleukin-10
• 819T/C
• Polymorphism
• Meta-analysis

• Case-Control Studies
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/genetics
• Crohn Disease/epidemiology
• Crohn Disease/genetics
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin-10/genetics
• Polymorphism, Single Nucleotide