Asthma is one of the most common disorders of respiratory tract, management of which still remains as a serious health problem. This study aimed to compare the efficacy of 3% hypertonic saline (HS) plus salbutamol with solely salbutamol on management of acute adults’ asthma based on peak flow meter findings. In this double-blind randomized clinical trial, 340 adult patients with acute asthma attacks admitted to emergency department of Ahvaz Golestan and Emam hospitals were enrolled during 2014-2015. The patients were allocated randomly to intervention group (nebulized 2.5 mg of salbutamol and 2.5 mL of 3% HS solution for three consecutive 20-min periods) and control group (nebulized only salbutamol in the same dose and time of the intervention group). The principal outcome measures were forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR), which were assessed at baseline, and 20, 40 and 60 minutes after treatment in both groups. HS plus salbutamol resulted in a significant increase compared with solely salbutamol in both PEFR and FEV1 in 40^th min (0.11±1.36; p=0.036 and 0.05±1.16; p=0.033, respectively) and 60^th min (0.15±1.12; p<0.001 and 0.11±1.22; p=0.011, respectively), while no significant difference was observed in baseline and 20^th min. Also, PEFR and FEV1 in both groups significantly increased as the treatment processed and the time passed. The results showed the beneficial effects of 3% HS in management of adults with acute asthma in the short term.

Asthma, affecting a growing number of populations, is a clinical condition with complex cellular and genetic factors. Single nucleotide polymorphisms (SNPs) in gene coding for molecules, which play major roles in the immunopathogenesis of asthma have been considered recently as genetic predisposing factors this disease. Possible association between two SNPs in a disintegrin and metalloprotease 33 (ADAM33), which participates in airway remodeling, and susceptibility to asthma was studied in this study. 190 patients with asthma and 180 healthy controls were enrolled in this case-control study. Using conventional PCR method, specific bands were amplified and the frequency of genotypes of T1 (rs2280091) and V4 (rs2787094) ADAM33 SNPs were determined by digestion with NcoI and PstI, respectively. The results showed that the frequency of genotypes of T1 and V4 were not significantly different between patients and controls (p=0.54 and p=0.85, respectively). On the other hand, no significant differences were seen in allele frequency of both T1 and V4 SNPs (p=0.15 and p=0.47, respectively). In agreement with some other studies in different populations, our results showed no association between frequency of genotype or alleles of both T1 and V4 SNPs in ADAM33 gene and predisposition to asthma in Azerbaijan population of Iran. Genetic differences in different ethnic groups might be involved in such inconsistent results. More studies in populations with larger number of patients and healthy individuals are needed for concluding remarks for involvement of ADAM33 SNPs in asthma. 

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization that lead to high morbidity and mortality among young infants. T helper 17 (Th17) cells and regulatory T cells (Tregs) play essential roles in the pathogenesis of autoimmune, cancer, and inflammatory diseases. However, whether changes in T-cell subsets are related to the systemic immune responses in RSV-caused bronchiolitis merit further investigation. Three-week-old Sprague Dawley (SD) rats were randomly divided into the normal control (NC) and RSV bronchiolitis (RSV-B) groups. An RSV-B model was successfully established using nasal drip containing RSV. Furthermore, pathological changes in the lung tissues were observed using hematoxylin and eosin staining. Flow cytometry determined the levels of Th17 and Treg subsets. The related cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of related transcription factors, such as RORγt and FOXP3, were examined using real-time quantitative PCR and western blot analysis. The RSV-B group exhibited pulmonary interstitial hyperemia and edema, inflammatory cell infiltration, wide alveolar septa, and bronchial collapse and deformation. The percentage of Th17 cells in RSV-B group was about 2.3 fold higher than that of NC group, and the concentration of IL-17, IL-23 and RORγt was higher than in NC group. In contrast, the percentage of Treg cells in the RSV-B group was approximately 0.7 fold lower than that in the NC group, and the levels of IL-10, TGF-β, and FOXP3 in the RSV-B group were lower than those in the NC group. The above results were statistically significant. The changes of Th17/Treg, and their associated cytokines, specific transcription factors, are present in RSV bronchiolitis model rats, which may play an important role in the pathogenesis of RSV bronchiolitis. 

The long lasting inflammation and immune dysregulation is one of the main mechanisms involved in lung complication of veterans exposed to sulfur mustard (SM) gas. Th17/Treg cells have an important role in immunopathogenesis of chronic obstructive pulmonary disease (COPD) and mustard lung disease. In this study, expression of cytokines genes levels related to Th17/Treg cells was determined in peripheral blood mononuclear (PBMC) of mustard lung patients and was compared with COPD patients and healthy controls (HC). Real time-polymerase chain reaction was used to assay genes expression levels of Th17 related cytokines (IL-17, IL-6 and TGF-β) and Treg related cytokines (IL-10, TGF-β). IL-17 gene expression level considerably was higher in SM patients (9.98±0.65, p<0.001), and COPD (4.75±0.71, p<0.001), compare to HC group. Also, gene expression level of IL-6 in the SM group (3.31±0.93, p<0.001) and COPD group (2.93±0.21, p<0.001) were significantly higher than the HC group. The IL-10 gene expression level showed a high increase in SM patients (4.12±0.91, p<0.01), and COPD (2.1±0.45, p<0.01). Finally, the TGF-β gene expression level was increased in SM patients (4.91±0.69, p<0.001) as well as in COPD group (5.41±0.78, p<0.001). In SM patients, IL-17 (R=-0.721, p<0.05), IL-6 (R=-0.621, p<0.05) and TGF-β (R=-0.658, p<0.05) had significant negative association with FEV1 (%). Inversely, Il-10 showed positive correlation (R=0.673) with FEV1 (%). Th17/Treg cells related cytokines genes were highly expressed and imbalanced in peripheral blood mononuclear cells of SM and COPD patients which correlated with pulmonary dysfunction.

The purpose of this study was to investigate the effects of interleukin-37 (IL-37) on a Dermatophagoides farinae (Der f)-induced murine model of allergic rhinitis (AR). BALB/c mice, except the control groups, were sensitized intraperitoneally and challenged intranasally with Der f (Der f group). The IL-37 and IL-37+anti-CD25 groups were administered IL-37 intranasally. The IL-37+anti-CD25 groups were administered anti-CD25 monoclonal antibody intraperitoneally before challenge. Allergic symptoms and the average eosinophil number were counted. The levels of cytokines and transcription factors in the nasal mucosa were measured by Real-Time polymerase chain reaction (PCR) and western blotting. The levels of Der f-specific immunoglobulin E (IgE) were measured. The CD4⁺CD25⁺Foxp3⁺T cells among splenic mononuclear cells were analyzed by flow cytometry. The allergic symptom scores and Der f-specific IgE levels were lower in the IL-37 group compared to the Der f group. Additionally, the levels of the transcription factor GATA-3 and ROR-γt and those of the cytokines IL-4, IL-5, IL-13, and IL-17, representing both T helper (Th)2 and Th17 responses, were lower in the IL-37 group in comparison with the Der f group. However, the Th1 responsewas not suppressed after administration of IL-37. IL-37 increased the IL-10 level; however, Real-Time PCR, western blotting, and flow cytometry results showed the limited action of IL-37 on CD4⁺CD25⁺Foxp3⁺T cells. This study demonstrates that intranasal IL-37 can suppress Th2 and Th17 responses in an AR murine model. Furthermore, these data suggest that IL-10 is increased, but CD4⁺CD25⁺Foxp3⁺T cells are not correlated with the IL-37-induced mechanism.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days. Cells were then polarized to M1 macrophages by lipopolysaccharide (LPS) and interferon-γ (IFNγ) for 24h. Monocyte purity and macrophage markers expression were analyzed by flow cytometry. Analysis of AHR mRNA expression was performed by SYBR Green real-time PCR. Our results showed that AHR expression is significantly down-regulated in M1 macrophages compare to monocyte-derived macrophages. It was shown that both monocyte-derived macrophages and M1 macrophages from BD patients significantly express lower level of AHR mRNA compared to healthy individuals. Our results demonstrate an anti-inflammatory role for AHR in macrophages, which suggest that decreased AHR expression is associated with pro-inflammatory M1 macrophage and BD susceptibility.

Type 1 diabetes (T1D) is the result of the autoimmune destruction of insulin-producing beta cells. Regulatory T cells (Tregs) and plasmacytoid dendritic cells (PDCs) act as mediators of peripheral tolerance. We investigated the possible alterations of such cells in peripheral blood of patients with T1D compared to normal individuals. This comparison may lead to a better understanding of the immunopathogenesis processes involved in T1D. 92 participants, including 49 patients with T1D and 43 healthy controls were studied. 3 mL of blood was taken from all participants. After isolating peripheral blood mononuclear cells (PBMCs), PDCs as well as 2 subtypes of Tregs, CD4⁺CD25⁺FoxP3⁺ and CD8⁺CD28^- cells were counted by 3-colorflow cytometry. The association between such enumeration and T1D was studied by multivariate regression and discriminate function models. The frequency of CD4⁺CD25⁺FoxP3⁺Tregs (p=0.038) and PDCs (p=0.039) in the peripheral blood of diabetic patients was less than that in healthy subjects. Having compared some models consisting different cells as well as their combinations, we did not find any profound explanation of each subset or their combinations to identify T1D. The decrease of CD4⁺CD25⁺FoxP3⁺cells and PDCs in diabetic patients may suggest their role in the onset or development of the disease. Therefore, it is likely that their pharmacologic stimulation may direct immune responses towards tolerance and prevent the development or even the onset of diabetes in susceptible individuals.

The aim of this study was to investigate the effect of β-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA) (identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters. Moreover, serum levels of TNF-α and IL-6 were analysed before and after M2000 therapy compared to healthy controls using enzyme linked immunosorbent assay method. We found a significant increase in the count of red blood cells and also hemoglobin (Hb) concentration (0.9 g/dL) in anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.01, respectively). Furthermore, our results showed an improvement in Hb level (0.45 g/dL) even in non-anemic patients who were treated by M2000 (p<0.04). The leukocytosis in RA patients, significantly decreased in both anemic and non-anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.03, respectively). The percent of neutrophils significantly increased in anemic patients (p<0.01) while in non-anemic patients it significantly decreased after 12 weeks of M2000 therapy (p<0.01). The serum levels of IL-6 and TNF-α significantly decreased after 12 weeks of M2000 therapy (p<0.01 and p<0.04, respectively). M2000 improves hematological parameters in RA patients by its potent inhibitory effect on serum levels of TNF-α and IL-6.

The aim of this study was to evaluate the effects of M2000, a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property and without gastro-nephrotoxicitic effects on matrix metalloproteinases (MMP)-2 and (MMP)-9 in phorbol myristate acetate (PMA)-differentiated THP-1 cells. Gene expression and activity of MMP-2 and MMP-9 are inhibited respectively by the tissue inhibitor of matrix metalloproteinase (TIMP)-2 and (TIMP)-1 and are induced by extracellular matrix metalloproteinase inducer (CD147/EMMPRIN). In this study, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine gene expression of MMP-2, MMP-9, TIMP-1, and TIMP-2. Flow cytometry and zymography were applied to determine cellular surface expression of CD147 and activity of MMP-2 and MMP-9, respectively. Our results showed that treatment of THP-1 cells with high concentration (25 µg/mL) of M2000 significantly decreased the cellular surface expression of CD147 (p<0.05) and the gene expression of MMP-2, MMP-9 and TIMP-1 (p<0.05), and inhibited the gelatinolytic activity of MMP-2 and MMP-9 (p<0.05). According to our results, M2000 can reduce inflammation through inhibition of the cellular surface expression of CD147 and decrease the gene expression and gelatinolytic activity of MMP-2 and MMP-9 in PMA-differentiated THP-1 cells.

Narcolepsy is a rare, disabling disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. Several studies demonstrated its association with HLA-DQB1*0602 in various ethnic groups. Our study aimed to determine the prevalence of HLA-DQB1*0602 allele in Iranian patients with narcolepsy and assess its predictive parameters for diagnosing narcolepsy. In addition, car accidents and job problems were assessed among narcoleptic patients. We studied 44 narcoleptic patients, 30 patients with other types of excessive daytime sleepiness (EDS)  and 50 healthy age and sex matched individuals in this case-control study. Patients and controls filled out a questionnaire including items about car accidents due to sleepiness and job problems. International classification of sleep disorders-2 criteria was used as the gold standard for diagnosis of narcolepsy. The DNAs isolated from whole blood samples were collected from the patients and controls to assess the presence of HLA-DQB1*0602. The results showed that HLA DQB1*0602 was present in 4 (8%) individual of controls and 20 (45.5%) patients with higher prevalence in patients with cataplexy (78.9%) than patients without cataplexy (p<0.001). The sensitivities of the DQB1*0602 for diagnosing narcolepsy with cataplexy and narcolepsy without cataplexy were 78.9 and 20; specificities were 88 and 72.4, respectively. 18.2% of patients had car accidents due to sleepiness and 68.2% suffered from job problems. Our study shows that evaluation of DQB1*0602 in patients suspected to narcolepsy could be helpful especially in complex cases with atypical cataplexy and indistinguishable multiple sleep latency test MSLT results. Moreover, high rates of car accidents and job problems are found among narcoleptic patients.

Unsuccessful Desensitization in a Child with Hypersensitivity to Diazoxide