Bee pollen grains, as the male reproductive part of seed-bearing plants contain considerable concentrations of various phytochemicals and nutrients. Since antiquity, people throughout the world used pollens to cure colds, flu, ulcers, premature aging, anemia and colitis. It is now well-documented that some bee pollen secondary metabolites (e.g. flavonoid) may have positive health effects. In recent years, the flavonoids have attracted much interest because of their wide range of biological properties and their beneficial effects on human health. The current review, points out potential therapeutic effects of bee pollen flavonoids as one of the main bee pollen bioactive compounds in allergic and immunological diseases. Due to the fact that some types of flavonoid components in bee pollen have anti-allergic, anti-oxidant and anti-inflammatory properties, bee pollen flavonoids can be excellent candidates for future studies including phytotherapy, molecular pharmacology and substitutes for chemicals used in treating allergic and immunological disorders.

Cow's milk allergy is the most common type of food allergy that decrease the quality of life of patients and their families. The aim of this study was to evaluate the efficacy of oral immunotherapy in patients with cow's milk allergy. 14 patients above 3 years of age with a history of cow's milk allergy confirmed by positive double blind placebo controlled food challenge (DBPCFC) test, presence of serum IgE against cow's milk and positive SPT (skin prick test) were enrolled in this study. During the immunotherapy all patients received increasing amounts of cow's milk during three phases. The type and severity of allergic reactions were recorded after each dose. The serum IgE and SPT were measured at the beginning and at the end of study. Since February 2014 to March 2015, 14 patients with the median age of 4.75 (3.7-7) years were studied. 13 patients (92.9%) completed the build up and maintenance phase successfully and became desensitized to cow's milk. During the build up and maintenance phase, 24 (2.0%) and 11 (0.9%) episodes of allergic reactions occurred, respectively. The median serum IgE level against cow's milk proteins and casein decreased from 39.3 to 10.4 and 7.72 to 2.83 (ku/L), respectively. The median of the difference of the wheal diameter in SPT with the control, decreased from 10 to 6 mm during the immunotherapy protocol. Oral immunotherapy is effective to decrease the frequency and the severity of allergic reactions but due to high rate of allergic reactions and possible anaphylaxis, it must be done under strict supervision of both clinicians and caregivers.

Taking medical history, physical examination, and performing some in vivo and in vitro tests are necessary for the diagnosis of allergy. Skin prick test (SPT) is considered as the standard method and first-line approach for the detection of allergic sensitization. Although mainly SPT is used for the detection of allergic sensitization, intradermal skin test (IDST) may be necessary, especially in patients with a negative SPT result. IDST is quite safe; however, is nowadays seldom used for detection of inhalant allergy and its value remains controversial. We aimed to investigate whether IDST is useful and necessary in diagnosis of respiratory allergies or not. This study involved 4223 patients with allergic rhinitis (AR) and/or bronchial asthma (BA). SPT results were positive in 2419 patients (57%) and negative in 1804 (43%). IDST was applied to 344 patients with marked allergic symptoms and with negative SPT results. Out of 344 patients, 152 (44%) showed allergic sensitization to IDST. The most commonly encountered allergic response was against the house dust mite (HDM) (32.6%). Allergic response against fungal spores was also relatively high (22%), while the pollen allergy rate (4.3%) was quite low. In BA patients with negative prick test, IDST made a significant contribution to the diagnosis of HDM allergy (p=0.003). To avoid missed diagnosis of AR and BA, particularly regarding  the HDM allergy, application of IDST may be beneficial; therefore, IDST should be considered as the next step after SPT for diagnosis of allergy prior to in vitro or provocation tests. 

The asthma treatment and control might be associated with significant burden on family and community‚ thus exploring other therapeutic plans could be desirable. The aim of this study was to investigate the effect of salt space on clinical findings and peak expiratory flow rate among children with asthma. In this randomized crossover trial, 34 patients aged 6-14 years old with mild to moderate asthma were selected and randomly divided into two groups. The first group went through a period of salt therapy by staying in the salt room for one hour, three times a week for 3 consecutive weeks and then was under observation for three weeks. This process was reversed for the second group (three weeks under observation followed by salt therapy). The wash-out period was one week. During the study, the morning and evening peak expiratory flow (PEF), the frequency of coughing, wheezing, dyspnea and use of rescue medications were measured. Salt therapy had a significant effect on raising the morning and evening PEF in the second week in both groups (p=0.028 and p=0.032, respectively). However, there was no significant effect on PEF variabilities‚ cough‚ wheezing, dyspnea, and the frequency of rescue medication (p>0.05). No side effect was observed during salt therapy. This study showed the significant effect of salt therapy on PEF rate of the patients in the second week. However, further studies with different frequency and time of salt therapy on respiratory disorders are recommended. 

Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x10⁶ BMSCs-injected group (Group II), non-BO, 1x10⁶ BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-γ IL-2 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.

Despite its proven efficacy, the hepatitis B vaccine requires improvements in immune enhancement and durability, especially in the elderly. Levamisole, an immune modulator, has been tested as an adjuvant to hepatitis B vaccine in several studies in immune-compromised populations. However, we aimed to evaluate the effect of levamisole on the immune response to hepatitis B vaccine in healthy subjects. In this randomized clinical trial, healthy family members of chronic hepatitis B patients were given twenty-microgram intramuscular injections of hepatitis B vaccine at 0, 1, and 6 months and 50 miligrams of oral  levamisole twice a day for two weeks with every vaccination dose. Serum hepatitis B surface antibody (HBsAb) levels of ultimately 98 individuals were measured one month after the final vaccination dose and compared to those of 119 subjects that received placebo and vaccine with an identical regimen. HBsAb levels >10 mIU/mL were considered protective. The Student’s t-test, Mann-Whitney test, Kruskal–Wallis analysis (quantitative comparison in age groups), Chi-square test, and the Pearson correlation were used to analyze data. p<0.05 was considered significant. Serum HBsAb levels were significantly higher in the test group (p<0.001). All test subjects had levels above 50 mIU/mL (86.7% exceeding 100 mIU/mL). The quantitative response according to age groups was remarkable (p=0.01 and p<0.001 for placebo and levamisole, respectively), while that of gender was insignificant (p=0.9). Unlike HBsAb titers amongst controls, levels in the levamisole group were affected by smoking (p=0.79 and p=0.006, respectively). We conclude that oral levamisole as an adjuvant to the hepatitis B vaccine enhances the anti-HBs antibody in healthy vaccinees. 

Skin dryness and thickening are hallmarks of systemic sclerosis (SSc) disease. Aquaporins (AQPs) are plasma membrane proteins that transport glycerol and water, resulting in water retention and skin hydration. Expression of AQPs has been evaluated in human normal skin. However, expression of these proteins in SSc dermal fibroblasts has not yet been reported. The aim of this study was to assess the expression profile of AQPs in dermal fibroblasts of SSc patients. Fibroblast cells were extracted from SSc and healthy skin biopsies and characterized using fibroblast surface protein antibody. The SYBR Green Real-time PCR was used to evaluate the mRNA expression of AQP1, 3, 5, 7, 9, and 10 in dermal fibroblasts. Immunoblotting was performed to confirm the results of Real-time PCR. Our data demonstrated that only AQP1, AQP3, and AQP9 were expressed in human skin fibroblasts. Moreover, the expression of AQP3 mRNA and protein were significantly decreased in SSc dermal fibroblasts compare to healthy fibroblasts. AQP3, which involves in skin hydration and wound healing through water and glycerol transmission, is downregulated in SSc fibroblasts. Based on previous studies and our results, it seems that SSc manifestations like skin dryness, abnormal wound healing, and fibrotic lesions may be related to downregulation of AQP3 in SSc fibroblasts. Therefore, induction of AQP3 expression can be a potential treatment to relieve SSc skin thickness in the future.

Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group. We showed that expression of Foxp3, transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) are increased in iTregs generated after miR-21 transfection in comparison with cytokine-differentiated iTregs and control group. Our findings demonstrate that miR-21 has positive role in in-vitro generation of induced regulatory T-cells (iTregs).

After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. DNA from 65 patients with biopsy-proven acute kidney allograft rejection (AKAR), 61 clinically stable graft function (SGF) recipients and 176 healthy subjects were identified for the presence or absence of 10 variable KIR genes (both activating and inhibitory receptors) and their HLA ligands using polymerase chain reaction-sequence specific primers (PCR-SSP) assay. Although no significant difference in the frequency of individual KIR genes, was found the gene content, and the haplotypic distribution between the three categories were detected, the frequency of the KIR3DL1+HLA-Bw4*A allele combination was significantly lower in AKAR patients compared to SGF recipients (p=0.004, OR=0.34, CI=0.16-0.72) and healthy subjects (p=0.019, OR=0.47, CI=0.25-0.89). Kaplan-Meier survival test showed that the KIR3DL1+HLA-Bw4*A allele combination could be considered protective for AKAR (p=0.04 by log-rank). The results of this study suggest that KIR/HLA polymorphism may be a genetic susceptibility factor to alloreactivity dysfunction in the NK cells of patients with AKAR. It is likely that a KIR/HLA combinatorial study can be beneficial in predicting AKAR occurrence for the purpose of selecting donors appropriately.

The effects of Portulaca oleracea and its constituent, alpha linolenic acid on serum oxidant levels and inflammatory cells in sensitized rats were examined. Eight groups of rats including control, sensitized, sensitized rats treated with 1, 2 and 4 mg/mL extract of P. oleracea, 0.2 and 0.4 mg/mL alpha linolenic acid (ALA) and 1.25 μg/mL dexamethaswere studied serum levels of superoxide dismutase (SOD), catalase (CAT, thiol groups, NO₂, NO₃, and Malondialdehyde (MDA) as well as total and differential WBC in blood were measured. Serum concentrations of SOD, CAT and thiol were significantly decreased but NO₂, NO₃ and MDA as well as total WBC number and percentages of eosinophil and neutrophil were increased in sensitized group (p<0.001 for all cases).Treatment of sensitized animals with dexamethasone, high concentrations of the extract and ALA improved all measured variables except monocyte for all three treatment groups and eosinophil for dexamethasone treatment (p<0.01 to p<0.001). In addition, treatment with low and medium extract and low ALA concentrations improved serum levels of NO₂, NO₃ and total WBC count (p<0.001 for all cases). Neutrophil and lymphocyte percentages and serum level of thiol also improved due to treatment with medium extract and low ALA concentration (p<0.01 to p<0.001). Medium extract and low ALA treatment also caused improvement of serum level of CAT and eosinophil percentage as well as SOD level respectively (p<0.01 to p<0.001). The effect of the extract of P. oleracea and ALA on serum oxidants and inflammatory cells were demonstrated in sensitized rats, which was comparable with dexamethasone effects at used concentrations.

The abnormal function of the T lymphocytes causes a range of autoimmune diseases, particularly multiple sclerosis; hence, several methods have been used to treat these disorders through the induction of antigen-specific tolerance in T cells. The present study aims to use a simple and low-cost method to produce poly (lactic-co-glycolic acid) (PLGA) nanoparticles for carrying antigens and inducing antigen-specific tolerance. In this study, PLGA nanoparticles were produced using the water/oil/water (W/O/W) method. The myelin oligodendrocyte glycoprotein (MOG) peptide and ovalbumin peptide(OVA) were covalently bound to the synthetic PLGA nanoparticles in the presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) and were injected to six groups of C57BL/6 mice one week before the induction of the experimental autoimmune encephalomyelitis (EAE) intravenously or subcutaneously; one group was considered as control; finally, immunologic responses including delayed-type hypersensitivity (DTH) response and lymphocyte proliferation were investigated. The results showed that the intravenous injection of microparticles containing MOG peptides before the development of the EAE model, not only could delay the incidence of syndrome, but also increase the antigen-specific tolerance. Moreover, a reduced delayed-type hypersensitivity response was observed in the mice primed with microparticles containing MOG peptides. In addition, a reduced spleen lymphocyte proliferation was found in the same mice when challenged with antigens. The present study proposes a simple, inexpensive, effective and safe method for preparing MOG-conjugated PLGA microparticles with immune tolerance properties that can be used in the treatment or reducing clinical syndromes of EAE model.