Biological and Immunological Aspects of Iron Deficiency Anemia in Cancer Development: A Narrative Review.

Iron Deficiency Anemia (IDA) is a universal health problem and a risk factor for the development of cancer. IDA changes the microenvironment of the human body by affecting both the biological and immunological systems. It increases DNA damage and genomic instability by different mechanisms. IDA is one of the leading causes of the imbalance between different antioxidant enzymes as well as enzymes involved in DNA damage and DNA repair systems of the body. It can affect the biogenesis/expression of microRNAs. IDA interrupts the oxidative phosphorylation energy metabolism and intestinal Cytochrome-P450 systems. It also disturbs multicellular signaling pathways involved in cell survival and helps in tumor angiogenesis. Moreover, IDA is also responsible for the functional deterioration of innate and adaptive immune systems that lead to immunological dysfunctions against invading pathogens. Genomic instability and immunological dysfunctions are the hallmarks of cancer development. In this review, we will review the evidence linking IDA to increased cancer risk.

Study of the tumor microenvironment during breast cancer progression.

BACKGROUND: Different cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy. METHODS: In this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4+ T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7. RESULTS: The results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression. CONCLUSION: We conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer.

Evaluation of TLR9 expression on PBMCs and CpG ODN-TLR9 ligation on IFN-α production in SLE patients.

CONTEXT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoreactive antibodies. Recent findings revealed the importance of innate immune responses, especially Toll-like receptors (TLRs) in the pathogenesis of SLE. OBJECTIVE: In this study, the level of TLR9 expression on peripheral blood mononuclear cells (PBMCs) was analyzed. The levels of produced IFN-α were also measured in supernatant of PBMCs from SLE patients and healthy controls after stimulation with CpG ODN2216 which is a plasmocytoid dendritic cell (pDC)-specific TLR9 ligand. MATERIALS AND METHODS: TLR9 expression was analyzed by real-time polymerase chain reaction (PCR) and flow cytometry in 35 SLE patients and 38 healthy controls and IFN-α concentration was measured in supernatants using enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that the TLR9 expression in the mRNA and the protein level was significantly higher in PBMCs from SLE patients. However, IFN-α concentration in patients and controls significantly increased in response to CpG stimulation but this increase was significantly higher in healthy controls compared with SLE patients. Our results do not show any association between taking hydroxychloroquine and reduction in IFN-α production in SLE patients. DISCUSSION AND CONCLUSIONS: Regarding the findings of the study, there is the possibility that TLR9 has played a role in SLE pathogenesis, and consequently it implies that TLRs can be considered to be the therapeutic targets for systemic autoimmunity. We may conclude that PBMCs in patients are functionally impaired in response to TLR ligation via innate response stimulating pathogen-associated molecular patterns (PAMPs).

Polycyclic aromatic hydrocarbons and childhood asthma.

Asthma is the most common chronic illness in children living in developed countries and the leading cause of childhood hospitalization and school absenteeism. Prevalence rates of asthma are increasing and show disparities across gender, geographic regions, and ethnic/racial groups. Common risk factors for developing childhood asthma include exposure to tobacco smoke, previous allergic reactions, a family history of asthma, allergic rhinitis or eczema, living in an urban environment, obesity and lack of physical exercise, severe lower respiratory tract infections, and male gender. Asthma exacerbation in children can be triggered by a variety of factors, including allergens (e.g., pollen, dust mites, and animal dander), viral and bacterial infections, exercise, and exposure to airway irritants. Recent studies have shown that exposure to polycyclic aromatic hydrocarbons (PAHs), a major component of fine particulate matter from combustion sources, is also associated with onset of asthma, and increasing asthmatic symptoms. In this paper, we review sources of childhood PAH exposure and the association between airborne PAH exposure and childhood asthma prevalence and exacerbation.

Effects of probiotic yogurt on fat distribution and gene expression of proinflammatory factors in peripheral blood mononuclear cells in overweight and obese people with or without weight-loss diet.

OBJECTIVES: The purpose of this study was to investigate whether probiotics had an effect on proinflammatory markers and cytokines in overweight and obese individuals and whether they could have synergistic effects with weight-loss diets. METHODS: A total of 75 healthy overweight and obese individuals completed this randomized doubled-blind controlled clinical trial. Participants were randomly assigned to groups consuming regular yogurt with a low-calorie diet (LCD, RLCD; n = 25) or receiving probiotic yogurt with LCD (PLCD; n = 25) or consuming probiotic yogurt without LCD (PWLCD; n = 25) for 8 weeks. The pribiotic regimen contained 200 g/day yogurt, enriched by Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 10(8) colony-forming units/g. Body fat percentage, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), leptin, and mRNA levels of inflammation-related genes (TNF-α and RAR-related orphan receptor gamma [ROR-γt]) in peripheral blood mononuclear cells (PBMCs) were measured. RESULTS: A reduction in body mass index (BMI), fat percentage, and leptin level was observed that was more obvious in groups who received the weight-loss diet with probiotic yogurt. Reduction in the gene expression of ROR-γt was significant in the PLCD group (p < 0.001). The expression of TNF-α did not change among all groups after intervention. The mean concentration of leptin was significantly decreased in all groups after the dietary intervention, but the mean changes in leptin level in the PLCD group was more prominent compared to the other two groups (-2.38, p < 0.001 [PLCD] vs -1.75, p = 0.002 [RLCD] and -0.55 ng/mL, p = 0.12 [PWLCD]). The reduction in serum levels of hs-CRP was more evident in the PWLCD group compared to the PLCD and RLCD groups after the 8-week intervention (-3.4, p = 0.03 vs -1.76, p < 0.001 and -2.98 pg/mL, p < 0.001, respectively). CONCLUSION: Our results suggested that the weight-loss diet and probiotic yogurt had synergistic effects on T-cells subset specific gene expression in PBMCs, fat percentage, and body weight among overweight and obese individuals.

Evaluating the reliability of Persian version of ankylosing spondylitis quality of life (ASQoL) questionnaire and related clinical and demographic parameters in patients with ankylosing spondylitis.

Ankylosing spondylitis quality of life (ASQoL) is an instrument for assessing quality of life (QoL). The aims of this study were to assess the reliability of Persian version of ASQoL questionnaire and evaluation of QoL status and related factors in ankylosing spondylitis (AS). One hundred and sixty-three Iranian patients with AS who fulfilled modified New York criteria were enrolled. Patients were evaluated using questionnaires including demographic and clinical variables, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), fatigue, Bath AS Metrology Index, pain and ASQoL. Reliability and validity of Persian version of ASQoL were evaluated by test-re-test agreement, internal consistency and correlation with specific scales. Relationship of parameters with ASQoL was analyzed by multiple regression. Age, disease duration and ASQoL score (mean ± SD) were 37.74 ± 9.88, 14.49 ± 8.47 and 8.02 ± 5.28 years, respectively. Test-re-test reproducibility for ASQoL was good as assessed by intra-class correlation coefficient (ICC: 0.97, P < 0.001). Internal consistency was high (Cronbach's alpha: 0.91). Convergent validity was confirmed by correlation of ASQoL score with specific scales (BASFI, r = 0.74, BASDAI, r = 0.6, fatigue, r = 0.56, depression, r = 0.24, intermalleolar distance, r = -0.44 and educational level, r = -0.37). Persian version of ASQoL is a valid and reliable scale to assess QoL in AS. Function, fatigue, mood, hip mobility and education are the factors which should be noted to achieve the best QoL.

Clinical characteristics and medical management of Iranian patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease with variable clinical expression. Ethnic, racial and geographical factors have been associated with disease occurrence and expression. We intended to describe the clinical characteristics and assess the disease severity and treatment status in Iranian AS patients. METHODS: A total of 320 AS patients were assessed for demographic variables, clinical manifestations, human leukocyte antigen (HLA) status, disease severity, functional capacities, quality of life and treatment status. RESULTS: A gender ratio of 3.8:1, an average age onset of 27 ± 7.3 and a mean diagnostic delay of 8 years were observed. Eleven percent had juvenile onset AS. Positive family history was higher than that observed in most other countries. Enthesitis was a very common finding involving more than two-thirds of our patients. Uveitis was the leading extra-articular manifestation. We found an HLA-B27 prevalence of 73% and four HLA-B27 subtypes. Disease activity was high and the functional status was poor as indicated by mean Bath AS Disease Activity, Functional and Metrology indices. Quality of life was considerably impaired in our patients. We found a low percentage of patients on biological medications and a relatively higher percentage on disease modifying anti-rheumatic drugs and corticosteroids. CONCLUSIONS: Our results demonstrate a broad characterization of Iranian AS patients providing a better understanding of this disease. A national multicenter registry would enable larger- scale prospective studies to be carried out further evaluating the disease burden on patients and society.

Evaluation of the Iranian versions of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Patient Acceptable Symptom State (PASS) in patients with ankylosing spondylitis.

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) are widely used instruments in assessment of patients suffering from ankylosing spondylitis (AS). The Patient Acceptable Symptom State (PASS) is regarded as a target for patients' well-being. The aim of this study was to translate and adapt BASDAI, BASFI and PASS into the Iranian official language, Farsi, and evaluate their reliability and validity. Ninety patients with AS were included in this study. The questionnaires were translated into Farsi and back translated into English, modified until the final versions were approved with minor adaptations and the VAS was changed to numerical rating scales from 0 to 10. Forty-eight-hour test-retest agreement showed good reliability: interclass correlation coefficient (ICC) for BASDAI was 0.93 (CI at 95%, 0.90-0.95), for BASFI was 0.96 (CI at 95%, 0.94-0.97) and for PASS was 0.87 (CI at 95%, 0.79-0.92). Chronbach's alpha was 0.95, 0.96 and 0.87 for BASDAI, BASFI and PASS, respectively. BASDAI showed a significant correlation with patient global disease activity index, nocturnal back pain, total back pain, number of swollen joints, number of enthesites, morning stiffness, Bath Ankylosing Spondylitis Global Score (BAS-G), BASFI and BASMI. A significant correlation was also found between BASFI and occiput-to-wall distance, mentum-to-sternum distance, chest expansion, finger-to-floor distance, number of swollen joints, number of enthesites, nocturnal back pain, total back pain, BAS-G, BASDAI and BASMI. Patients who answered "no" to PASS (found their condition unsatisfactory) reported significantly increased pain scores, patient global disease activity scores, BAS-G, BASDAI and BASFI scores. The results showed that the Iranian versions of BASDAI, BASFI and PASS are adequately reliable and valid in patients with AS.

Natural killer cells in allergic rhinitis patients and nonatopic controls.

BACKGROUND: Allergic rhinitis (AR) is currently considered to be a worldwide problem. The role of type 2 cytokines in this disease has been established, and natural killer (NK) cells are possibly the source of cytokine secretions. This study was performed to confirm the existence of type 2 cytokine-secreting NK cells in AR patients and to determine their characteristics. METHODS: Twenty AR patients and 20 healthy nonatopic controls were included. Peripheral blood mononuclear cells were separated from heparinized blood by density gradient centrifugation. NK cells were enriched and cultured for 72 h. Cytokine secretion was measured by ELISA, and cytotoxicity assay was carried out using the PKH2-labeled K562 cell line. Intracytoplasmic cytokine staining and an analysis of surface markers of NK cells were performed on freshly isolated peripheral blood mononuclear cells using flow cytometry. RESULTS: Patients with AR had a higher percentage of NK cells compared to nonatopic subjects. The mean percentage of IL-4+ NK cells was significantly higher and that of IFN-γ+ NK cells was nonsignificantly lower in AR patients compared to healthy nonatopic controls. IL-13 secretion was also significantly higher in AR patients compared to nonatopic controls. While there was no difference between the case and the control groups with regard to the surface expression of CD40, CD45RO, and CD95, the expression of CD178 was significantly higher in the cases when compared to the controls. NK cell cytotoxicity was also significantly higher in AR patients compared to healthy controls. CONCLUSIONS: This study confirms the existence of type 2 cytokine-secreting NK cells in AR and shows their increased number and enhanced cytotoxicity compared to normal individuals.

20 Years from the Establishment of Iranian Journal of Allergy, Asthma and Immunology.

No abstract.

Effect of food intake and ambient air pollution exposure on ankylosing spondylitis disease activity.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial arthritis. The genetic-environmental factors seem to be involved in the pathogenesis of the disease and the disease debilitates patients during the most productive stages of their lives. The aim of this study was to examine the relationships between two environmental factors, diet and air pollution with disease activity and functional impairment in AS. METHODS: A case-control study was carried out. Thirty patients with AS and 30 age and sex-matched healthy controls were included. Disease scores including BASMI, BASDAI, BASFI, and BASG were calculated by means of the international Ankylosing Spondylitis Assessment working group consensus recommendations. The food intake was evaluated by semi-quantitative food frequency questionnaire (147 items FFQ). Level of air pollution indices, PM10 and PM2.5 information was obtained from the Tehran air quality control network. RESULTS: Total energy and fat intake, some vitamins (A, B1, B2, C) and mineral intake (potassium, calcium, iron, phosphorus, magnesium, zinc, copper and selenium) were significantly higher in patients with AS compared to controls. Fat component consumption especially Saturated Fat of Food was moderately correlated with BASFI score. PM2.5 long term exposure was strongly correlated with BASMI, BASFI and BASDAI scores of patients. CONCLUSION: High-fat diet and long term exposure to air pollution are associated with worse disease outcomes reported in patients with AS. This is an interesting area of investigation in AS pathogenesis and management.

Paediatric asthma prevalence: The first national population-based survey in Iran.

BACKGROUND: The actual prevalence of paediatric asthma as a worldwide chronic disease has been surveyed in developed countries. However, no sufficient survey has been conducted in most of the eastern developing countries. Herein, we took measures to evaluate the prevalence of paediatric asthma in Iran. METHODS: In this national cross-sectional study, the prevalence of asthma symptoms was estimated throughout the country using a randomized multistage stratified cluster sampling method in 16 410 and 16 850 individuals aged 6-7 and 13-14 years, respectively. A validated questionnaire including core questions of the International Study of Asthma and Allergies in Childhood (ISAAC) was applied between November 2015 and February 2016. RESULTS: The total prevalence of asthma was 10.9% (n = 3624) (95% confidence interval [CI]: 10.6%-11.2%) which was significantly higher among 13- to 14-year olds compared to a younger age group (12.4% vs. 9.4%, P < 0.001), males versus females (12.1% vs. 9.8%, P < 0.001) and residents of urban compared to rural areas (P = 0.003). The prevalence of severe asthma was 3.9%, being significantly more prevalent in higher age groups and male individuals (P < 0.001). A significant relationship was found between asthma and passive smoking in both 6- to 7- and 13- to 14-year olds (P < 0.001). CONCLUSIONS: The prevalence of asthma and severe asthma in the paediatric population of Iran was similar to other developing countries. It is recommended to pay special attention to urban regions, male individuals and higher age groups for better controlling of asthma. Nevertheless, further national surveys are necessary to determine the trend of paediatric asthma in Iran.

Overweight adolescents: a group at risk for metabolic syndrome (Tehran adolescent obesity study).

BACKGROUND: Metabolic syndrome not only is a serious problem for adults, but is also afflicting an increasing number of children and adolescents. This syndrome is a risk factor for type 2 diabetes mellitus and cardiovascular diseases. The aim of this study was to estimate the prevalence of metabolic syndrome in a sample of Iranian adolescents. METHODS: A total of 554 overweight adolescents (aged 11 - 17 years) participated in a community-based cross sectional survey. Anthropometric examinations including height, weight, body mass index, and blood pressure were assessed. A fasting blood sample was taken for measurement of glucose and lipid profile. Metabolic syndrome was determined by the definition released by the National Cholesterol Education Program Adult Treatment Panel III, which was modified for age. RESULTS: The overall prevalence of metabolic syndrome was 26.6%. There was no gender difference in the distribution of metabolic syndrome. When stratified by body mass index, 22.5% were overweight (BMI> or =95th percentile) besides having the criteria for metabolic syndrome, while the remaining 4.1% of the adolescents were at risk for overweight (BMI between 85th and 95th percentile) together with metabolic syndrome. Hypertriglyceridemia was the most common and high-density lipoprotein was the least common constituent of metabolic syndrome. CONCLUSION: This study suggests a high prevalence of metabolic syndrome among overweight Iranian adolescents. This poses a serious threat to the current and future health of Iranian youth.

The prevalence of asthma in Iranian adults: The first national survey and the most recent updates.

BACKGROUND: The worldwide increase in the prevalence of asthma has made it a major public-health concern. We aimed to identify the prevalence of asthma and asthma symptoms in adults living in urban and rural areas of Iran as a populated country with about 80 millions of residents. METHODS: This cross-sectional study was conducted to estimate the prevalence of asthma in adults between 20 and 44 years old in all provinces of Iran. Data were collected by personal interview via a standardized questionnaire [European Community Respiratory Health Survey (ECRHS)] between November 2015 and February 2016. RESULTS: A total of 24 344 individuals were enrolled. The prevalence of asthma was 8.9% [95% confidence interval (CI): 8.5-9.3]. The most common asthma symptoms were wheezing (14.2%, n = 3465), nocturnal cough (13.3%, n = 3234) and chest tightness (11.3%, n = 2760). Additionally, the prevalence of current asthma (taking asthma medications or asthma attack) was estimated to be 4.7% (n = 1155). Asthma was significantly more prevalent in males compared to females (P = .002), while no significant relationship was detected between gender and asthma after adjusted analysis with other variables. The prevalence of asthma was significantly higher in older participants (P < .001) and individuals with low educational level (P < .001). Interestingly, there was no significant relationship between asthma and area of residency (P = .8). CONCLUSIONS: The prevalence of asthma in Iran was similar to other Asian and European countries. However, repeated national surveys are required to determine the trend of asthma prevalence in Iran in comparison to other countries.

Pain in ankylosing spondylitis: a neuro-immune collaboration.

Clinicians have commonly differentiated chronic back pain into two broad subsets: namely, non-inflammatory (or mechanical) back pain and inflammatory back pain. As the terminology suggests, the latter category, in which ankylosing spondylitis (AS) is prominent, presupposes a close link between pain and inflammation. Advances in research into the genetics and immunology of AS have improved our understanding of the inflammatory processes involved in this disease, and have led to the development of potent anti-inflammatory biologic therapeutic agents. However, evidence from clinical trials and from biomarker and imaging studies in patients with AS indicate that pain and inflammation are not always correlated. Thus, the assumption that pain in AS is a reliable surrogate marker for inflammation might be an over-simplification. This Review provides an overview of current concepts relating to neuro-immune interactions in AS and summarizes research that reveals an increasingly complex interplay between the activation of the immune system and pain pathways in the nervous system. The different types of pain experienced by patients with AS, insights from brain imaging studies, neurological mechanisms of pain, sex bias in pain and how the immune system can modify pain in patients with AS are also discussed.

Frequency and Risk Factors of Penicillin and Amoxicillin Allergy in Suspected Patients with Drug Allergy.

BACKGROUND: Unconfirmed beta-lactam allergy is a significant public health problem because of the limitations it imposes in drug selection. In this study, we aimed to evaluate patients referred for beta-lactam allergy to determine the frequency of confirmed beta-lactam allergy and identify some risk factors. METHODS: In a prospective cohort study, all referred patients to Immunology, Asthma and Allergy Research Institute in Tehran University of Medical Sciences (between 2007 - 2009) who suspected to have beta-lactam allergy were entered into this study based on having the inclusion criteria. Follow-up was performed 6 - 8 years after the final diagnosis. Diagnosis of beta-lactam allergy relies on thorough history and specific IgE measurements (ImmunoCAP), skin prick testing (SPT), intradermal testing (IDT), patch testing, and oral drug challenge test. RESULTS: Fifty-one patients with mean age of 24.5 (±18.5) years were enrolled in this study. Based on workups, beta-lactam allergy was confirmed in 16 (31.4%) patients, suspicious in 22 (43.1%) patients and ruled out in 13 (25.5%) patients.  During the follow-up, 3 patients with suspicious drug allergy consumed the culprit drug with no reaction so allergy was finally ruled out in 16 (31.4%) patients. Age, sex, atopy and family history of drug allergies were not significantly different between the patients with confirmed or ruled-out diagnosis of penicillin and amoxicillin allergy. CONCLUSION: At least up to one-third of patients with a history of beta-lactam allergy are proven to be safe using the drug. Also, a clear protocol consists of serum sIgE assay and SPT can be helpful to the physicians in the health care system.

MicroRNAs in rheumatoid arthritis.

The role of genetic and epigenetic factors in the development of rheumatic diseases has been an interesting field of research over the past decades all around the world. Research on the role of microRNAs (miRNAs) in rheumatoid arthritis (RA) has been active and ongoing, and investigations have attempted to use miRNAs as biomarkers in disease diagnosis, prognosis, and treatment. This review focuses on experimental researches in the field of miRNAs and RA to present the data available up to this date and includes researches searched by keywords "microRNA" and "rheumatoid arthritis" in PubMed from 2008 to January 2015. All references were also searched for related papers. miRNAs are shown to act as proinflammatory or anti-inflammatory agents in diverse cell types, and their role seems to be regulatory in most instances. Researchers have evaluated miRNAs in patients compared to controls or have investigated their role by overexpressing or silencing them. Multiple targets have been identified in vivo, in vitro, or in silico, and the researches still continue to show their efficacy in clinical settings.

Gastroesophagial reflux disease and asthma in pregnant women with dyspnea.

Asthma and gastroesophageal reflux disease (GERD) are two common problems in pregnancy and they affect pregnancy in several ways. In this study, we aimed to evaluate GERD and asthma in pregnant women who referred for prenatal care visits. One-hundred and seventy three pregnant women with a complaint of dyspnea were included in the study. A questionnaire was filled and lung function tests were performed. All patients were visited by a respiratory specialist and questionnaires were evaluated by a gastroenterologist. Out of the total number of women studied, 37% were diagnosed to have asthma and 36.4% were non-asthmatics. Twenty six percent of the pregnant women who had symptoms and signs of asthma with normal spirometry were classified as probable to have asthma. GERD was diagnosed in 80.9% of the pregnant women, but it was not significantly higher in asthmatic or probable asthmatic women compared to non-asthmatic ones. However, severity of GERD was significantly higher in asthmatic pregnant women compared to the others. In conclusion, the prevalence of GERD was quite high in pregnant women, irrespective of the fact that they were asthmatic or non-asthmatic. Further studies evaluating women throughout pregnancy will inform us more about this relationship.

The effects of high fat, low carbohydrate and low fat, high carbohydrate diets on tumor necrosis factor superfamily proteins and proinflammatory cytokines in C57BL/6 mice.

There has been considerable inconsistency regarding the potential relationship between dyslipidemia and bone metabolism. The inflammatory stimulation through the receptor activator of the nuclear factor kappa-B ligand (RANKL)/ receptor activator of the nuclear factor kappa-B (RANK)/ osteoprotegerin (OPG) pathway could be the infrastructural mechanism for hypercholesterolemia-induced bone loss.In this study, we investigated the effect of dyslipidemia on RANKL and OPG alongside with pro-inflammatory cytokines. Thirty male C57Bl/6 mice (4 weeks old) were randomized to two purified diet groups (15 animals in each group), high fat, low carbohydrate diet (HFLCD) and its matched low fat, high carbohydrate diet (LFHCD). After 12 weeks of feeding in standard situations, the plasma concentration of lipid profile, interleukin (IL) 1Beta, IL-6, tumor necrosis factor-alpha (TNF-α) and RANKL, OPG, and RANKL: OPG ratio were measured.In the present study, although the body weight significantly increased during 12 weeks in HFLCD and LFHCD groups, there were no significant differences in food intake, food efficiency ratio and weight gain between the two groups. The LFHCD group had significantly higher median RANKL and RANKL/OPG ratio. There was no significant difference in plasma IL-1ß, IL-6 and TNF-α concentration between LFHCD and HFLCD groups.These unexpected findings from LFHCD, that seem to be as a result of its higher carbohydrate proportion in comparison to HFLCD, implicate dietary carbohydrate rather than dietary fat as a more significant nutritional factor contributing to change in RANKL level and RANKL: OPG ratio.

The role of interleukin-23 in stability of in vitro T helper-17 cells.

Interleukin (IL)-17-producing T helper (Th)-17 cells have recently been explained as a distinct population of CD4+ T cells which play an important role in immunity against infectious agents. Establishment of persistent phenotype of Th17 cells and recognition of lineage-deviating factors are of most attractive goals in modern researches in immunology. Although IL-6 and TGF-ß are frequently used to differentiate naive T cells to Th17 phenotype in mouse models, the application of IL-23 and its importance in preventing cells from plasticity needs to be more investigated. Our main objective was to evaluate the role of IL-23 in Th17 to Th1 plasticity. In this research project, we generated in vitro Myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells in the presence of TGF-ß, IL-6, IL-23 and peptide MOG35-55. Th17 development was confirmed by assessment of relevant transcription factors and secreted cytokines by flowcytometry and ELISA, respectively. Th17 to Th1 plasticity was monitored by consecutive samplings in different time points without any extra supplementation of IL-23. Cell culture supernatant was evaluated for Interferon (IFN)-γ secretion and cells were evaluated for intracellular expression of this cytokine. Our results showed that the employed method was relatively convenient in developing antigen-specific Th17 cells. We also showed that IL-23 deprivation which happens by prolongation of culture period, can convert IL-17 producing cells to IFN-γ secreting Th1 phenotype. IL-23 can be considered as a Th17 phenotype stabilizing factor for in-vitro developed lineages.