Hongyan Xu; Yueqing Yang; Qianhong Wu; Yan Zhang
Abstract
Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration ...
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Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration of PD-L1 in the pleural effusions for prediction of MDR-TB. Methods: We measured the ratio of Th2 to Th1 T cells from pleural effusions in 373 tuberculous pleuritis patients. We also measured the concentration of programmed death ligand-1 (PD-L1) in the pleural effusions of these patients. Afterwards, we determined the optimal cut-off value for predicting the occurrence of multi-drug resistant tuberculous based on the Youden index, diagnostic evaluation test, and receiver operation curve. Multiple logistic analysis was employed to identify the independent risk factors for MDR-TB occurrence. Results: The area under the curve (AUC) of the Th2 to Th1 ratio was 0.66 and the concentration of PD-L1 was 0.71. Based on the combined detection of PD-L1 concentration in pleural effusion and the Th2 to Th1 ratio, our AUC was 0.81 and had a specificity of 0.92. Only a combined detection was able to identify patients developing multidrug-resistant tuberculosis. Multiple logistic analysis showed that a high concentration of PD-L1 and a high Th2 to Th1 T ratio in pleural effusions were indicative of an immunocompromised status. Therefore, these measurements might be independent risk factors for the occurrence of multidrug-resistant tuberculous. Conclusion: Evaluation of immune status based on PD-L1 pleural concentration and Th2 to Th1 ratio might predict the risk of MDR-TB occurrence.
Reza Feyzi; Mohammad Hossein Boskabady; Seyedeh Masoumeh Seyed hosseini Tamijani; Houshang Rafatpanah; Seyed Abdolrahim Rezaei
Abstract
Background: Several biological and medical benefits of Saffron, Crocus sativus
(Iridaceae), have been demonstrated. However, mechanisms of actions for purified
constituents are greatly unknown. Objective: To examine the effects of Safranal, a main
constituent of Saffron stigma, on cell viability and ...
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Background: Several biological and medical benefits of Saffron, Crocus sativus
(Iridaceae), have been demonstrated. However, mechanisms of actions for purified
constituents are greatly unknown. Objective: To examine the effects of Safranal, a main
constituent of Saffron stigma, on cell viability and cytokine profile of peripheral blood
mononuclear cells (PBMC) were examined. Methods: Effects of Safranal at 0.1, 0.5
and 1 mM concentrations were evaluated on cell viability and production of interleukin
4 (IL-4), IL-10 and interferon-γ (IFN-γ) from non-stimulated and phytohemagglutinin
(PHA) stimulated PBMCs, compared to 0.1 mM dexamethasone and saline. Results: In
stimulated cells, different concentrations of Safranal caused significant decrease of
lymphocytes viability (p<0.001 for all concentrations). All concentrations of Safranal
inhibited IFN-γ and IL-10 secretion in stimulated cells (p<0.01). In addition, high
concentration of Safranal significantly decreased cell viability of non-stimulated
PBMCs (p<0.001). The effect of 1 mM Safranal on IL-4 secretion was less than
dexamethasone (p<0.05). Safranal showed a stimulatory effect on IFN-γ secretion in
non-stimulated cells. The IFN-γ/IL-4 ratio at the presence of two higher Safranal
concentrations both in non-stimulated and stimulated cells were significantly higher
than those of control and PHA stimulated groups, respectively (p<0.05). Conclusion:
The IFN-γ/IL-4 ratio increases in the presence of Safranal which indicates an effect on
Th1/Th2 balance. Therefore, Safranal may have therapeutic effects in inflammatory
diseases associated with Th1/Th2 imbalance.
Forooz Peiravian; Hamid Rajaian; Afshin Samiei; Nasser Gholijani; Behrouz Gharesi-Fard; Pooneh Mokaram; Abbas Rahimi-Jaberi; Eskandar Kamali Sarvestani
Abstract
Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles ...
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Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles of pro-inflammatory, Th1-, Th2-, and Th17-related cytokines were compared by quantitative multiplexed ELISA-based chemiluminescent assay in 44 RR-MS and 44 healthy age- and sex-matched individuals from the same ethnicity. Results: Among pro-inflammatory cytokines, the levels of IL-6 (p=0.003), IL-8 (p=0.05) and TNF-α (p=0.002) were higher in patients than controls, though IL-4 and IL-10 as well as ΣTh2 cytokines were lower in patients (p=0.05, p=0.02 and p=0.05, respectively). After gender classification, the higher levels of IL-4 in male patients remained significant and IL-13 also showed significantly higher levels in male patients compared to male controls (p=0.003 and p=0.05, respectively). A significant negative correlation was detected between EDSS and IL-10 or ΣTh2 levels (p=0.005). In addition, IL-1α (r=0.4, p=0.05) and IFN-γ (r=0.35, p=0.05) were also directly correlated with EDSS in female patients. Conclusions: Patients with RR‑MS who are in the relapse clinical phase exhibit higher levels of pro-inflammatory cytokines and reduction in protective Th2-related cytokines.
Linge Li; Bin Hu; Juan Feng; Yu Zhang; Xi Shou; Yu Tian; Chunrong Jiang; Hua Zhang
Abstract
Background: H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis. Objective: To establish the H2-Eb1 knockout ...
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Background: H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis. Objective: To establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in H2-Eb1 knockout mice as a model of AR. Methods: The Cre/LoxP system and ES gene knockout technology were applied to create heterozygous H2-Eb1 (+/-) knockout mice and their offspring of knockout homozygous(-/-), heterozygous (+/-) and wild type (+/+) H2-Eb1 mice. After identification, offspring of heterozygous (+/-) and homozygous (-/-) H2-Eb1 knockout mice were randomly selected to establish AR models to demonstrate the role of H2-Eb1 in AR pathogenesis. Results: The H2-Eb1 knockout mice model was successfully established. The reproduction and feeding of the homozygous ( -/-) H2-Eb1 knockout mice were successful. Compared with the control group, the serum OVA-IgE and IL-4 levels significantly increased, while IFN-γ levels significantly dropped (p<0.05) in the experimental groups. For the two experimental groups, the homozygous ( -/-) mice group had lower serum OVA-IgE and IL-4 levels, and higher IFN-γ levels than their heterozygous (+/-) counterparts (p<0.05), concomitant with slighter allergic symptoms (gentle behavior and less eosinophils in nasal mucosa). Conclusion: Our study demonstrated that knockout of H2-Eb1 gene could alleviate mouse AR Symptoms, indicating H2-Eb1 may play an important role in regulating Th1/Th2 balance during the pathogenesis of AR.
Nowruz Delirezh; Ehsan Shojaeefar
Abstract
Background: Generation of an effective dendritic cell (DC) based cancer vaccine depends on appropriate differentiation of monocytes in vitro. Objective: To compare the effects of monocyte separation methods, flask adherence (Flask-DC) and magnetic activated cell sorting (MACS-DC), on phenotypic and functional ...
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Background: Generation of an effective dendritic cell (DC) based cancer vaccine depends on appropriate differentiation of monocytes in vitro. Objective: To compare the effects of monocyte separation methods, flask adherence (Flask-DC) and magnetic activated cell sorting (MACS-DC), on phenotypic and functional characteristics of resultant DCs. Methods: DCs from healthy volunteers were generated from plastic adherence and MACS isolated monocytes in the presence of GM-CSF and IL-4 as well as TNF-α and monocyte conditioned medium (MCM) in 7 day cultures. Mature DCs were then subjected to phenotypic analysis using anti-CD14, anti-CD83 and HLA-DR monoclonal antibodies. Functional and cytokine release assays were carried out using [3H] thymidine uptake test and commercially available ELISA kits for the determination of IL-12, IL-10, IFN-γ and IL-4, respectively. Results: We found that MACS-DCs were more homogenous and the yield and viability were fairly higher than Flask-DCs. MACS-DCs expressed higher levels of CD83 and HLA-DR as well as CD14 compared to the Flask-DCs. Induction of T cell proliferative responses were higher in Flask-DCs and also they elicited higher levels of IL- 12: IL-10 and IFN-γ: IL-4 ratios in cytokine generation assays. Conclusion: MACS method was superior for mass production of viable homogenous and fully mature DCs but their cytokine profile had the potential to polarize the immune system toward Th2 type immune response.
Alireza Andalib; Hassan Doulabi; Mohammadreza Najafi; Mehdi Tazhibi
Abstract
Background: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine ...
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Background: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine expression pattern of these lymphocyte subsets. Objective: This study was performed to measure chemokine receptor expression on CD4 T cells for evaluation of Th1/Th2 dominantly in IFN-β treated patients. Methods: flowcytometry was used to detect chemokine receptor expression on CD4 T cell population in PBMCs obtained from MS and healthy control groups. Twenty six MS patients participated in this study before and after IFN-β therapy and the same number of healthy individuals were included. Results: The percentage of lymphocytes was 41.28% ± 10.30 in the blood of MS group compared with 36.88% ± 5.51% in the control group (p=0.017). The CD4+CXCR3+ cells were 18.86% ± 8.46% in healthy group, 30.78% ± 9.8% in pre-treated MS patients and 21.06% ± 9.23% in posttreated group (p<0.001). The CD4+CCR4+ cell subsets were 27.35% ± 10.15% in healthy group; 28.17% ± 8.9% in pre-treated group and 34.20% ± 8.96% in the post- IFN-β treatment group. The subset of CD4+CCR4+ was found to be dominant after IFN- β therapy in comparison with the control group (p<0.001). CD4+CCR5+ percentage was 1.24% ± 0.92% in the healthy people, 1.23% ± 0.71% in the MS patients and 0.76% ± 0.49% in post-treatment status (p=0.003). CD4+CCR3+ cell subsets were 0.62% ± 0.67% in control group, 0.28% ± 0.26% in the MS patients (p=0.022) and 0.39% ± 0.54% in IFN-β treated patients (p=0.334). An association was found for CXCR3 expression in pre- and post- treatment status (r=0.840, p<0.001) as well as for CCR4+ expression (r=0.712, p<0.001) in the same groups. The Th1 response was dominant in pre-treatment states, and then it shifted to a Th2 dominant state after IFN-β treatment. Conclusion: We suggest that the chemokine receptor expression of Th1/Th2 cell subsets could be used for monitoring and the evaluation of the MS disease status.
