Iranian Journal of Allergy, Asthma and Immunology
Volume:11 Issue: 2, Jun 2012

Herbal medicines have been used for centuries to treat different illnesses. Among more than 20,000 herbal medicines available for humans, a limited number have sufficiently been studied and numerous remained to be investigated for their efficacy in treating human diseases. A number of herbal products are in use for their immunosuppressive effects. This capacity of herbs may have useful applications in immune-mediated disorders including autoimmune diseases and organ transplant rejection. Plants such as Salvia miltiorrhiza and Tripterygium wilfordii has been shown to reduce inflammatory cytokines and mediators, indicating their value in the treatment of acute graft rejections and autoimmunity. Tanacetum parthenium inhibits the release of pro-inflammatory mediators from macrophages and lymphocytes and Curcuma longa down regulates the expression of cytokines and chemokines as well as the transcription factor NF-kappaB. There has been growing interest to investigate novel anti-inflammatory or immunosuppressive activities from various sources particularly herbal medicines. This review focuses on the plants that have recently received more attention regarding their influence on the immune system, being reported as immunosuppressive and anti-inflammatory agents and promising protective effects for immune-mediated diseases.

Toll-Like Receptor 4 (TLR4), considered one of the most important TLR, recognizes lipopolysaccharide of gram-negative bacteria. Recognition of ligands by TLRs induces signaling pathways resulting in activation of transcriptional factors such as NF-κB which are involved in the expression of inflammatory cytokines and chemokines. To prevent an inappropriate immune response, a complex network of molecules negatively regulates TLRs and their associated signaling pathways. Two cosegregating single nucleotide polymorphisms of the human TLR4 gene, namely Asp299Gly and Thr399Ile, have been associated with hyporesponsiveness to inhaled LPS. The purpose of this study was to determine the impact of TLR4 gene variant on NF-κB activity in colorectal cancer cell line. HCT116 cells were transfected with wild-type and mutants Flag-CMV1-TLR4 expression vectors. Western blot analysis was performed to evaluate selected molecules involved in TLR4 signaling. NF-κB activity was assessed by dual-luciferase reporter assay and cytokine profiles were evaluated byELISA and Cytometric Bead Array method. Results showed that the activity of pNF-κB was higher in cells harboring TLR4 D299G compared to the other cells. However, the activity of pAKT, pERK1 and pIRAK was higher in wild-type. The results of cytokine measurements showed about four fold higher level of IL-8 in cells with wild-type TLR4. This study suggest that TLR4 Asp299Gly gene variant has an impact on TLR4 signaling and potentially on intestinal homeostasis due to impaired control signals at the epithelial cell level which may lead to chronic intestinal inflammation and interrupted intestinal homeostasis and may eventually lead to colorectal cancer.

In traditional Chinese medicine, arsenous compounds, including arsenic trioxide (ATO), are often used to treat many diseases, which are safe and effective. Recently, studies have indicated that Th17- IL-17 involved in the pathogenesis and development of asthma. The goal of this study was to investigate the effect and mechanism of ATO on asthma, especially the Th17- IL-17 axis.We used oval bumin (OVA)-immunized mice as a model for asthma and treated mice with ATO or dexamethasone. The mice were then monitored airway responsiveness, airway inflammation, mucus production, IL-17 levels in BALF and the positive rate of Th17 cells. In vitro, CD4+ T cells from splenic cell suspensions were separated and purified. We measured the expression of IL-17 and caspase-12 protein in purified CD4+ T cells, and detected IL-17 levels in CD4+ T lymphocyte culture solution with or without ATO. Moreover, apoptosis, mitochondrial membrane potential, cytosolic calcium were analyzed. We found that ATO could reduce airway responsiveness, airway inflammation, mucus hyperplasia, the expression of IL-17 in BALF and the positive rate of Th17 cells at a level comparable to treatment with DXM. In vitro data suggested that ATO can induce CD4+ T cells apoptosis, cause mitochondrial dysfunction, Ca2+ overload and promote caspase-12 activation. Our study suggested that ATO had potential medical value for the treatment of human asthma.

Oral allergy syndrome (OAS) is occasionally observed following consumption of raw fruits in allergic adults. Since this phenomenon was commonly reported in Khorasan province of Iran; we intended to check if common diagnostic tests could be applied for differential diagnosis of OAS to grapes.IgE reactivity of 84 patients with OAS to grape and 34 patients with OAS to other fruits were analyzed by in vivo and in vitro methods, and the results were compared with those of controls. The patients underwent skin prick test (SPT) with common allergic pollen extracts as well as grape extract. The specific IgE level to grape proteins was determined by an indirect ELISA. The correlation of SPT results with ELISA and western blotting patterns was checked by statistical methods. The results showed a significant correlation of grape SPT diameters with grape specific IgE levels. Furthermore, a significant association of grape SPT results with IgE immunoreactivity of a 10 kDa grape protein, probably lipid transfer protein (LTP) was prominent. Immunoreactivity of other proteins was linked with mild clinical symptoms. The study showed a significant correlation of grape SPT results with grape total extract, as well as its 10 kDa component's IgE reactivity. The results suggested that OAS to grape should not be considered as a main criterion in diagnosis of grape allergy and a combination of grape SPT results with evaluation of IgE reactivity to grape 10 kDa allergen should be considered to achieve a more reliable grape allergy diagnosis.

Allergy to wheat is a common food allergy. In spite of this fact, there is not enough literature regarding the features and outgrowing of this allergy. The objective of this study was to evaluate the manifestations of this allergy and to follow the patients to evaluate whether outgrowing allergy happens again and when it occurs.Eight wheat allergic patients diagnosed between 2000 and 2001 were re-evaluated together with 13 other new cases of wheat allergy referred to the Immunology and Allergy Pediatric Department from June 2004 to March 2006. For all cases, the demographic data along with a complete history regarding allergy to wheat and other types of allergy were collected in questionnaires. The specific IgE measurements (in vivo and in vitro) and oral food challenge (in the absence of a relevant history related to allergy to wheat) were performed. Severe anaphylaxis was seen after wheat ingestion in more than 90% of the patients. Oral tolerance to wheat developed in three patients (37.5%) out of 8 known previous cases who had been followed for eight years, the mean age of oral tolerance to wheat was 68±6.36 (range; 36 months to 108 months).Clinical reactions in our wheat-allergic patients were more severe than those reported before. These patients were at risk for developing chronic allergic symptoms such as asthma. We also found that oral tolerance to wheat was happening in a minority of our patients.

Fumonisins, a family of mycotoxins, are mainly toxic and carcinogenic. The present study was carried out to evaluate fumonisin B1 (FB1) effects on the production of inflammatory cytokines by gastric and colon cell lines. The study was performed on two cell lines under in vitro condition, including gastric epithelial cell line (AGS) and human colon adenocarcinoma cell line (SW742). Lipopolysaccharide (LPS) was used for inflammatory cytokine induction. The culture medium was supplemented with 4.5-72 mg/l of FB1 for 72 h before cell induction. The supernatants were harvested 24 h after the induction and measured for cytokines by using enzyme-linked immunosorbent assay.FB1 induced a dose-dependent increase in the production of tumor necrosis factor-α and interleukin-1β in both AGS and SW742 cell lines. This increase was statistically significant with concentration of FB1 between 9 and 72 mg/l (P < 0.05). FB1 also induced a dose-dependent decrease in interleukin-8 production. This decrease was seen in both cell lines and showed a statistical significance with FB1 concentration (P < 0.05).The results show that FB1 increases inflammatory cytokines production by various gastric and intestinal cells. This effect in the long run can possibly be the basis for the occurrence or development of inflammation and subsequent atrophy in the above-mentioned tissues.

Specific local immunotherapy has been recently introduced as an alternative to classic subcutaneous immunotherapy in treatment of allergic rhinitis. In this study, the effects of sublingual immunotherapy (SLIT) on symptoms and medication score and skin prick test evaluation of patients with allergic rhinitis were investigated.In this placebo controlled trial, twenty four patients aged 5-18 years old with grass pollen induced rhinitis and sensitive to rye grass by positive skin prick test received randomly sublingual extract of rye grass or placebo for 6 months. Symptom and medication scores and adverse effects of SLIT were assessed during treatment. Skin prick test induced wheal at the beginning and the end of therapy were also measured. Data were analyzed with SPSS software.We found significant reduction of symptoms in intervention group from 21st week of immunotherapy (p<0.05). Medication scores were also reduced after 16th week (p<0.05), adverse effects were low and insignificant in both groups. Erythema induced diameter with skin prick test for grass and rye grass was significantly reduced in SLI group after immunotherapy.This study indicates that SLIT in grass-pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumes. We recommend this therapy as a safe therapy in patients with allergic rhinitis.

Lactic acid bacteria which are used as probiotics have ability to modulate immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors. In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp casei was orally administered to the test mice and it was followed 3 weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner. Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (P<0.05) and increased the natural killer cells (NK) cytotoxicity in spleen cells culture of test mice (P<0.05). It has also been demonstrated that the growth rate of tumor in the test mice was decreased and their survival was significantly prolonged in comparison to the controls. Our findings suggest that daily intake of L.casei can improve immune responses in mice bearing invasive ductal carcinoma, but further studies are needed to investigate the other involving mechanisms in this case.

The purpose of the study was to evaluate interleukin-6 production, in saliva-activated mononuclear cell cultures from malocclusion patients, before and after placement of. 014 NiTi archwires.Four patients receiving. 014 Nitinol archwire to correct malocclusion participated in this study. Samples of their blood and saliva were collected before and after placement of the apparatus. Mononuclear cells were obtained from the blood using the Ficoll-Paque (1.077 g/ml) density gradient separation method. Mononuclear Cells were activated with saliva from each patient and were cultured in 96-well plates for 72 hours. Samples were collected at 24 hours before apparatus placement, and at 24 hours and 72 hours after placement. IL-6 expression levels in the cell culture supernatants were quantified by ELISA. An increase in IL-6 levels in the cell culture supernatants was observed 24 hours after placement of the orthodontic apparatus relative to the negative control (p= 0.002) and IL-6 came to basal limits 72 hours after apparatus placement.IL-6 quantification may be useful as a biomarker to estimate the inflammatory response caused by forces applied during orthodontic treatment and their levels came to basal limits 72 hours after apparatus placement in patients without systemic diseases. The isolation of saliva components involved in such effects is important to study the mechanisms to control the acute inflammation in oral cavity after apparatus placement.