The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is associated with sepsis susceptibility, whereas G allele is associated with higher stimulated interleukin-10 production and increased mortality in severe sepsis.

No abstract

A wide array of studies has demonstrated differences in genotype and allele frequencies of cytokine gene polymorphisms depending on ethnicity and race. In this study, the frequency of Taq-I polymorphism in 3 0 untranslated region of IL-12B was investigated in two Bulgarian ethnic groups-Bulgarians and Turkish minority. No significant differences of genotype and allele frequencies were observed between these groups. Genotype distribution in the total group of Bulgarian citizens was: AA (61%), CA (32%) and CC (7%), and the allele frequency of 16974 A allele was 0.77. We also evaluated whether this polymorphism affects IL-12p40 production from human PBMC after stimulation. We demonstrated that association between genotype and IL12p40 production by stimulated PBMC depends on the stimuli used. Our results indicated a significantly decreased IL-12 p40 secretion for the following order of genotypes: AA4CA4CC, after stimulation of PBMC with C3-binding glycoprotein (C3bgp) in contrast to lipopolysaccharide, phytohaemagglutinin and pokeweed mitogen.

Colorectal cancer (CRC) development is strongly associated with innate immune mechanisms and intestinal inflammation. The aim of the study was to investigate the pre-operative serum levels of TNF-α and its correlation with cancer progression and survival in CRC patients taking into account the genotype of –308G/A promoter polymorphism in TNF-α gene (rs1800629). TNF-α –308G/A genotypes of 119 CRC cases and 177 no CRC controls were determined by restriction fragment length polymorphism assay (RFLP-PCR). TNF-α serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Although no significant differences in allele and genotype frequencies between CRC and controls were observed, it should be noted that the minor allele-A and its homozygous genotype were overrepresented among CRC. In addition, allele-A was more frequent in early CRC patients compared to advanced cases. TNF-α serum level was significantly higher in CRC patients than in controls (36.1 ± 8.4 pg/mL vs. 18.66 ± 11 pg/mL; p = 0.0000001). In the subgroup analysis by tumour–node–metastasis stages, the highest TNF-α level was found in stage IV (42.7 ± 12.5 pg/mL) and was significantly elevated compared to earlier stages of CRC and controls. The survival rate of CRC patients with low TNF-α serum level, estimated as median survival, was significantly higher than that of patients with high levels of TNF-α (38.4 vs. 7.761 months; log rank test p = 0.00015) In conclusion, we can affirm that TNF-α affects tumour development along with disease progression which has an impact on the survival of CRC.

No abstract

The role of functional polymorphism within IL10 (rs1800896) in colorectal cancer (CRC) still remains elusive. The aim of present study was to investigate the significance of -1082A/G polymorphism in IL10 on CRC risk, progression, and overall survival in a cohort of Bulgarian patients. Also, a functional role of this polymorphism on systemic and local level of IL10 mRNA quantity and serum IL-10 level was explored. A group of 119 patients with sporadic CRC and 154 age-sex-matched controls were genotyped by allele-specific PCR. The quantification of mRNA and serum IL-10 levels was performed by real-time PCR and ELISA assays, respectively. The genotype and allelic frequency among cases and controls was similar. However, we observed significant elevation of G-allele and GG-genotype frequencies among advanced CRC. G-allele was overrepresented in advanced CRC patients (49 %) compared to early CRC (35 %) with OR = 1.77; 95%CI 1.018 ÷ 3.083; P = 0.031. A significant upregulated expression of IL10 mRNA was observed among AG/GG-genotypes in tumor tissue compared to homozygous AA-genotype (RQ value 68.3 vs. 6.68; P = 0.0062). Also, GG-genotype of -1082A/G polymorphism in IL10 was positively associated with higher serum IL-10 among early CRC patients and controls, in contrast to advanced cases. Although, investigated polymorphism in IL10 has no significant impact of overall survival among Bulgarian CRC patients, we found a significant relationship of high pre-operative serum level of IL-10 with poor survival of CRC (P = 0.023). Our findings indicate a significant impact of -1082A/G polymorphism of IL10 on CRC progression, rather than genetic predisposition and prognosis of CRC.

The viability of PBMC at the onset of sepsis and enhanced production of IL-12 and diminished production of IL-10 after stimulation with all stimuli used may be a favorable prognostic factor in sepsis.

Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients' quality of life, independently from the course and phase of the disease. The relationship between pathological brain findings and cognitive impairment is a subject of intensive research. Summarizing recent data about prevalence, clinical specificity and treatment of cognitive disorders in MS, this review aims to motivate the necessity of early diagnosis and complex therapeutic approach to these disturbances in order to reduce the social burden of the disease.