Vol 15, No 3 (2016)

Original Article(s)

  • XML | PDF | downloads: 733 | views: 1117 | pages: 167-173

    Promoter polymorphism of cytokine genes may lead to inter-individual differences in cytokine levels, therefore, polymorphisms may associate with susceptibility to infectious diseases. In this study, we investigated a possible association between interleukin-10 (IL-10) -1082A⁄G (rs1800896) and interferon (IFN)-gamma +874T/A (rs2430561) promoter polymorphisms and tuberculosis (TB) in the Azeri population of Iran. IL-10 -1082G/A and IFN-gamma +874T/A single nucleotide polymorphisms (SNPs) were genotyped by amplification refractory mutation system (ARMS)-PCR in 200 healthy controls and 124 tuberculosis patients. IL-10 -1082 A allele was more frequent in the control group than in the patient group (p=0.001, odds ratio [OR]=2.183). On the other hand, the AA genotype was significantly more frequent in the control group (p=0.0001). The frequency of IFN-gamma +874 T allele was significantly higher in the controls (p=0.013, OR=1.56). There was no significant association between IFN-gamma +874 T/A genotypes and susceptibility to tuberculosis (p=0.078), but TT genotype was more frequent in the control group. Our findings suggest that interleukin-10 -1082G/A polymorphism may play an important role in susceptibility to tuberculosis in our population. On the other hand, the +874T allele, which has been suggested to be associated with high IFN-gamma levels, was significantly higher in the controls and TT genotype was also more frequent in the control group. Thus, +874 T allele may be associated with resistance to tuberculosis in this Azeri population of Iran.

  • XML | PDF | downloads: 725 | views: 1289 | pages: 174-182

    Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients.

  • XML | PDF | downloads: 6799 | views: 860 | pages: 183-197

    Epidemiological and clinical studies indicate a close relationship between obesity and asthma. Here, we determined the impact of diet-induced obesity on the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA as well as IL-1β protein level and pathological changes in male Wistar rat’s lung after sensitization with ovalbumin (OVA). Twenty male Wistar rats divided into four groups, control with normal diet (C+ND), OVA-sensitized with normal diet (S+ND), control with high-fat diet (C+HFD), and OVA-sensitized with high-fat diet (S+HFD). All rats fed for 12 weeks with standard pellets or high-fat diet while sensitization and challenging with OVA or saline were done for groups in the last month. In the end of intervention, lung was isolated and tested for the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA with real time-PCR method, and pathological changes were determined. Diet-induced obesity groups showed increased weight, obesity indexes and lipid profiles The expression levels of IL-1β mRNA in OVA-sensitization groups (S+ND and S+HFD) showed a significant increase compared with other groups. Also in S+HFD group, expression level of IRAK-1 and TRAF-6 mRNA were markedly higher than other groups (p<0.001). The pathological changes were marked in sensitized groups compared to non-sensitized groups; with marked increase in obese sensitized rat. The results showed that high fat diet caused overexpression of IL-1β, IRAK-1 and TRAF-6 mRNA as well as IL-1β protein in an experimental model of asthma. Our results suggest that obese-asthmatic conditions may lead to the local production and activation of pro-inflammatory agents.

  • XML | PDF | downloads: 815 | views: 1264 | pages: 198-203

    There has been a great increase in the consumption of various food additives in recent years. The purpose of this study was to identify the incidence of sensitization to food additives by using skin prick test in patients with allergy and to determine the concordance rate between positive skin tests and oral challenge in hypersensitivity to additives. This cross-sectional study included 125 (female 71, male 54) patients aged 2-76 years with allergy and 100 healthy individuals. Skin tests were performed in both patient and control groups with 25 fresh food additives. Among patients with allergy, 22.4% showed positive skin test at least to one of the applied materials. Skin test was negative to all tested food additives in control group. Oral food challenge was done in 28 patients with positive skin test, in whom 9 patients showed reaction to culprit (Concordance rate=32.1%). The present study suggested that about one-third of allergic patients with positive reaction to food additives showed positive oral challenge; it may be considered the potential utility of skin test to identify the role of food additives in patients with allergy.

  • XML | PDF | downloads: 650 | views: 654 | pages: 204-211

    Previous studies have demonstrated that vascular endothelial growth factor (VEGF) can trigger angiogenesis as well as inflammation through binding to its membranous receptor-1 on endothelial and inflammatory cells. We aimed to correlate the circulatory number of cells expressing such receptor as well as the serum level of VEGF and the soluble form of its receptor-1 (sVEGFR1) to the severity of multiple sclerosis (MS). This case-control study was done on 102 cases of MS lacking any other inflammatory or pathologic conditions and 75 healthy volunteer subjects. The severity of MS was examined by expanded disability status scale (EDSS). The serum levels of VEGF and sVEGFR1 were measured by ELISA, and the circulatory frequency of VEGFR1 expressing cells was counted by flowcytometry. Then, the correlation of these variables was evaluated by pearson’s correlation coefficient and spearman’s test. We also investigated the influence of sex, age, treatment duration, and the number of recurrences on such association through linear multivariate regression method. We found an increase in circulatory level of VEGFR1 expressing cells and the serum level of VEGF as well as sVEGFR1 in MS patients compared to healthy controls (p<0.001). The greater severity of MS, the higher VEGFR1 expressing cells (ρ=0.47; p<0.001), serum level of VEGF (ρ=0.44; p<0.001), and sVEGFR1 (ρ=0.76; p<0.001). Having adjusted the effects of VEGF on sVEGFR1, we found a significant association between the EDSS score and sVEGFR1 (β=0.007; p<0.001). Our findings revealed that circulatory membranous as well as soluble expression of VEGFR1 increases during angiogenic and inflammatory phenomena of MS. Such increase may exacerbate the symptoms and cause more disability.

  • XML | PDF | downloads: 1175 | views: 1466 | pages: 212-219

    Several religions recommend periods of fasting. One of the most frequently asked questions of MS patients before the holy month of Ramadan is weather fasting might have an unfavorable effect on their disease course. This debate became more challenging after the publication of experimental studies suggesting that calorie restriction prior to disease induction attenuates disease severity. We conducted this study to assess early and late effects of fasting on the animal model of MS, known as autoimmune encephalomyelitis. EAE was induced in the C57BL/6 mice, using Myelin Oligodendrocyte Glycopeptide  (MOG) 35-55 and they fasted every other day either after the appearance of the first clinical sign or 30 days after disease induction for ten days. Thereafter, the mice were sacrificed for further histological and immunological evaluations. Intermittent fasting after the establishment of EAE did not have any unfavorable effect on the course of disease. Moreover, fasting at the early phase of disease alleviated EAE severity by ameliorating spinal cord demyelination. Fasting suppressed the secretion of IFN-γ, TNF-α and raised IL-10 production in splenocytes. Fasting was also associated with a lower percent of cytotoxicity. Intermittent fasting not only had no unfavorable effect on EAE but also reduced EAE severity if started at early phase of disease.

  • XML | PDF | downloads: 391 | views: 563 | pages: 220-228

    Many studies have shown that cytotoxic T lymphocyte antigen-4 (CTLA-4) gene variants are associated with several autoimmune diseases particularly type 1 diabetes. Due to the lack of consistent data for this association with type 2 diabetes (T2D), this study explored the possible influence of CTLA-4 gene polymorphisms at -1722 (T/C), -318 (C/T), and +49 (G/A) positions for susceptibility to T2D in relation with neuropathy. One hundred and eleven unrelated patients with T2D [49 patients with diabetic peripheral neuropathy (DPN) and 62 patients without PDN] and 100 healthy ethnic- and gender-matched controls were included in this study. The dimorphisms at -1722 (C/T), -318 (C/T) and +49 (A/G) for CTLA-4 gene were determined using ARMS-PCR. The CTLA-4 (+49 G/G) and (+49 A/A) genotypes were found to be positively and negatively associated with T2D, respectively (p=0.03). The -318 C/T and T/T genotypes were more frequent in patients than controls and -318 C/C genotype was shown to be protective for T2D (p=0.003). ACT and GTT Haplotypes were less and more frequent in controls and patients, respectively (p=3.86×10-7 and p=2.29×10-5). Genotypes distribution among T2D patients with and without DPN compared to healthy controls showed significantly lower frequencies for -318 C/C and +49 A/A genotypes and significantly higher frequencies for -318 C/T and T/T genotypes as well. Our findings indicate that CTLA-4 (+49 A/G) and (-318 C/T) genotypes could be considered as genetic risk factors associated with susceptibility or protection for T2D.

  • XML | PDF | downloads: 797 | views: 1384 | pages: 229-236

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which results in damage to various organs. Some animal studies have revealed that activation of Toll-like receptors (TLRs) is important in the pathogenesis of SLE. In the present study, the percentage of different immune cell subsets in 35 SLE patients and 38 control subjects was analyzed by flow cytometry. We also assessed the expression of TLR9 in the population of peripheral blood mononuclear cells (PBMCs) including T lymphocytes (CD4+ and CD8+), B lymphocytes (CD19+), NK cells (CD56+) and monocytes (CD14+) in SLE patients and healthy controls. The results showed that the percentage of CD8+ T lymphocytes and CD14+ monocytes were significantly higher (p˂0.001) in the SLE patients than the healthy control subjects. Moreover, the percentage of CD56+ NK cells were significantly lower in the SLE patients than the healthy control subjects (p=0.001). The findings indicated that the expression of TLR9 was significantly higher in CD4+ and CD8+ T lymphocytes and CD19+ B lymphocytes of SLE patients than in control subjects (all p˂0.05). The difference in TLR9 expression are involved in pathogenesis of the SLE, hence it can be used as an indicator for SLE diagnosis.

  • XML | PDF | downloads: 8075 | views: 764 | pages: 237-243

    Henoch–Schönlein purpura (HSP), a common allergic hemorrhagic disease, occurs frequently in children affecting kidney, joint and skin. While interleukin-8 (IL-8) plays an important role in inflammation, the association between IL-8 gene +781 C/T polymorphism and HSP remains unclear. Interleukin-8, an important chemokine related to the initiation and amplification of acute inflammatory responses, has been reported to be involved in the pathogenesis of some autoimmune and inflammatory diseases. In this study, we aimed to investigate whether IL-8 gene +781 C/T (rs2227306) polymorphism has an influence on susceptibility and clinical manifestations of patients to HSP. This hospital-based case-control study comprised 192 patients with HSP and 202 healthy controls. The genotypes of IL-8 gene +781 C/T polymorphism were identified using PCR-TaqMan method. All genotype frequencies of both groups (patients and controls) conformed to the Hardy–Weinberg equilibrium. No significant differences in allele or genotype frequencies of IL-8 gene +781 C/T polymorphism were observed between patients with HSP and controls (p=0.98, χ2=0.000 and p=0.49, χ2=1.432, respectively). When patients were stratified for the presence of joint, gastrointestinal and renal manifestations, genotype frequencies of IL-8 gene polymorphism were found no statistically significant differences (p>0.05). Our findings do not support that IL-8 gene +781 C/T polymorphism has an effect on the susceptibility to HSP in Chinese children.

  • XML | PDF | downloads: 576 | views: 836 | pages: 244-250

    Measles, mumps and rubella are viral infectious diseases that may result in serious complications. Since the production of vaccines, the number of cases of these diseases has been dropped. Nevertheless, these infectious diseases are still one of the major health problems in developing countries. In this study, in order to evaluate the protective responses against measles, mumps and rubella, the level and avidity of virus-specific IgG antibodies were measured in 53 medical students of Tehran University, aged between 20-30 years. Except for mumps vaccine, all the students had been vaccinated against measles and rubella according to Iran’s nationwide mass vaccination protocol for all persons aged 5–25 in 2003. Our results showed that 96.2% of the volunteers had a protective level (>15 IU/ml) of IgG against rubella, 79.2% had a protective level (>11 IU/ml) of IgG against measles and 64.16% had a protective level (>11 IU/ml) of IgG against mumps. Over ten years after nationwide measles-rubella vaccination campaign, most young adults aged 20-30 had protective levels of humoral immunity against measles and rubella. However, Iranian young population is still unvaccinated against mumps, and therefore relatively large number of young adults had no protective level of IgG against it. This finding may be due to reduction in circulating of wild strain. We recommend screening of medical students for immunity against infectious agents such as measles, mumps, rubella, because they are at a high risk of these infectious agents.

  • XML | PDF | downloads: 671 | views: 1012 | pages: 251-256

    Multiple sclerosis (MS) is a complex, demyelinating disease of the central nervous system (CNS) with variable phenotypic presentations, while Guillain-Barre Syndrome (GBS) is the prototypic acute inflammatory disorder that affects the peripheral nervous system. Myasthenia gravis (MG) is a T cell dependent and antibody mediated autoimmune disease. Although it has been shown that complement plays a critical role in the pathogenesis of MS, GBS, and MG, the role of mannose-binding lectin (MBL) as a biomarker of immunopathogensis of these diseases and also its association with the severity of them have been poorly investigated. Therefore, in this study we aimed to measure plasma levels of MBL in patients with MS, GBS, and MG. In a case-control study, plasma was obtained from healthy controls (n=100) and also patients with MS (n=120), GBS (n=30), and MG (n=30). Plasma level measurement of MBL was performed using enzyme-linked immunosorbent assay (ELISA). The mean serum level of MBL was significantly different between groups of patients and healthy controls (p<0.001). We also found a positive correlation between plasma levels of MBL and severity scores of MS, MG, and GBS patients including: expanded disability status scale (EDSS) (r=+0.60 and p=<0.001), quantitative myasthenia gravis score (QMGS) (r=+0.56 and p=0.01), and GBS disability scale (GDS) (r=+0.37 and p=0.04). Taken together, our findings suggest that complement activation mediated by MBL contributes to the pathogenesis and also severity of MS, MG, and GBS. However, because the lectin pathway can be involved in several phases of the immune response, further evidence will be required to elucidate the underlying mechanism.