Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice.

Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)2D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D3 [25(OH)D3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D3 and were challenged with the influenza virus. In the lungs of 25(OH)D3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D3 suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.

Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot-and-mouth disease vaccine.

In the present study, the adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in serum and muscle tissue after intramuscular injection of SO-GS-R. The results showed that injection of SO-GS-R significantly increased the levels of IL-1ß, IL-5, IL-6, G-CSF, KC, MCP-1, MIP-1α, and MIP-1ß in both serum and muscle. These results suggested that SO-GS-R recruits neutrophils, eosinophils, T cells and macrophages, causing immune cell recruitment at the injection site, driving antigen-presenting cells to actively participate in the onset of immunity, and amplifying the immune responses. Considering its adjuvant activity and plant-derived properties, SO-GS-R should be further studied for its adjuvant effect on vaccines used in food animals.

Theobroma cacao extract attenuates the development of Dermatophagoides farinae-induced atopic dermatitis-like symptoms in NC/Nga mice.

Cacao beans from Theobroma cacao are an abundant source of polyphenols, particularly flavonoids. Previous studies demonstrated that cacao flavanols decrease pro-inflammatory cytokines resulting in the alleviation of allergic symptoms. We sought to investigate the effects of cacao extract (CE) on Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like symptoms. CE attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Histopathological analysis revealed that CE suppressed DFE-induced immune cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum immunoglobulin (Ig) E, chemokine; thymus and activation-regulated chemokine and macrophage-derived chemokine as well as the skin-derived cytokines interleukin (IL)-4, IL-5, and interferon-γ. CE also significantly alleviated transepidermal water loss and increased skin hydration. These results suggest that CE, a natural phytochemical-rich food, has potential therapeutic efficacy for the treatment of AD.

Antiviral effects of Yinhuapinggan granule against influenza virus infection in the ICR mice model.

Yinhuapinggan granule (YHPG), a Chinese medicine granule based on Ma-Huang-Tang (Ephedra Decoction) and the clinical experience of Professor Wan Haitong, is used in traditional Chinese medicine (TCM) for the treatment of colds, influenza, fever, inflammation and cough. This study investigated the antiviral effects of YHPG on the production of inflammatory cytokines in influenza virus (IFV)-infected mice and evaluated the effect of YHPG on the expression of NF-κB p65 and the level of key signaling molecules in the TLR4 signaling pathway. ICR mice were orally administrated YHPG at doses of 7.5, 15 and 30 g kg(-1) day(-1) for 2 or 6 days after IFV infection. On days 3 and 7 after infection, YHPG (15 g/kg and 30 g/kg) significantly increased levels of interleukin (IL)-2 and interferon gamma and decreased levels of IL-4, IL-5 and tumor necrosis factor (TNF) in serum compared with the IFV control group. Furthermore, the expression of TLR4, MyD88, TRAF6 and NF-κB p65 at the mRNA and protein level was significantly lower in the YHPG (15 and 30 g/kg) treatment groups than in the IFV control group. These results suggest that YHPG has antiviral effects in IFV-infected mice, which is associated with the inhibition of the TLR4-MyD88-TRAF6 signaling pathway and the expression of NF-κB p65.

Rapeseed oil and ginseng saponins work synergistically to enhance Th1 and Th2 immune responses induced by the foot-and-mouth disease vaccine.

Previous investigations demonstrated that saponins isolated from the root of Panax ginseng C. A. Meyer (i.e., ginseng root saponin [GS-R]) had adjuvant activity. In the present study, the combined effects of rapeseed oil (RO) and GS-R on the immune responses elicited by foot-and-mouth disease (FMD) vaccine were investigated by measuring FMD virus (FMDV)-specific antibody levels, cytokine levels, lymphocyte proliferation, and long-lived IgG-secreting plasma cells from bone marrow in a mouse model. The results indicated that RO in combination with GS-R significantly enhanced serum IgG and isotype concentrations, gamma interferon (IFN-γ) and interleukin 5 (IL-5) levels, splenocyte proliferative responses to stimulations with concanavalin A (ConA), lipopolysaccharide (LPS), and FMDV antigen, and the numbers of IgG-secreting plasma cells in the bone marrow, suggesting that RO/GS-R enhanced both Th1 and Th2 immune responses. In addition, no significant difference was found between RO/GS-R and the commercial adjuvant oil ISA 206 in the promotion of FMD vaccine-induced immune responses. Considering the vegetable origin of RO and GS-R and the potent adjuvant activity, RO/GS-R should be studied further for the development of veterinary vaccines, especially for use in food animals in order to promote food safety.

Novel approaches to food allergy.

Food allergies have increased in recent decades. However, they cannot be effectively treated by the current management, which is limited to the identification and avoidance of foods that induce allergies and to the use of medicines for symptoms relief. To meet the medical need of prevention and cure of food allergies, several therapeutic strategies are under investigation. Some newly developed biologics such as anti-IgE antibody and anti-interleukin (IL)-5 antibody directed against significant molecules in the allergic process have shown their potential for the treatment of food allergies. Allergen-specific immunotherapy is the therapy that induces immune tolerance and may reduce the need for conventional medication, severity of allergic symptoms and eliminate hypersensitivity. In this article, clinical studies of immunotherapy via subcutaneous, oral, sublingual, and epicutaneous routes are extensively reviewed for their safety and effectiveness on various food allergies. In addition, to reduce the risk of anaphylaxis and increase toleragenic immunity, many studies are focusing on the modification of traditional allergens used for immunotherapy. Moreover, a Chinese herbal formulation with potential anti-allergic effects is being evaluated for its efficacy in patients with peanut allergy. Although more studies are needed, accumulated data of current studies represent compelling evidence of curative effects of some strategies and give a hope that food allergies are likely to be successfully treated in the future.

Suppression of allergic reactions in ovalbumin-sensitized mice by yam storage proteins dioscorins.

To study the biomedical functions of dioscorins isolated from various species of Dioscorea , we investigated their antiallergic potential using an OVA-induced allergy mouse model. All the dioscorins suppressed allergic reactions by decreasing the serum IgE and histamine levels. The serum IFN-γ and IgG2a levels increased in all the dioscorin-treated mice. The spleen cells from the dioscorin-treated mice also exhibited an up-regulation of IFN-γ secretion in response to ConA stimulation. Although dioscorins did not affect the IgG1 levels, the IL-5 levels decreased to basal levels in mice treated with dioscorins of D. alata or D. japonica and in most of the lymphoid cells of the dioscorin-treated mice in response to ConA stimulation. The decrease of IgE and histamine levels was concomitant with an increase in IFN-γ and IgG2a levels and with a decrease in IL-5 levels, suggesting that dioscorins suppressed the OVA-induced allergic reactions, possibly through modulating an imbalanced Th1/Th2 immune response.

Chemistry and biology of oligovalent ß-(1→2)-linked oligomannosides: new insights into carbohydrate-based adjuvants in immunotherapy.

A series of oligovalent carbohydrate assemblies (ranging from mono- to pentavalent), derived from three structurally different ß-linked or ß-(1→2)-linked mannosides, has been chemically synthesized, and the respective compounds have been biologically evaluated in order to investigate their immunostimulatory properties. The Crich methodology for ß-mannosylation was successfully utilized to introduce the ß-linkages, and a click chemistry protocol was utilized to generate the oligovalent derivatives. A convenient protecting group strategy involving the simultaneous use of both p-methoxybenzyl and benzylidene groups was employed, which allowed a simple and cost-effective global deprotection step. The immunomodulatory properties of the synthesized multivalent mannosides were evaluated by assessing cytokine production in human white blood cell cultures. The Th2-type cytokines interleukin-4 and interleukin-5 (IL-4 and IL-5), the Th1 cytokine interferon-γ (IFN-γ), the Treg cytokine IL-10, and the pro-inflammatory cytokine tumor necrosis factor (TNF) were included in the screening. A single trivalent acetylated mannobiose derivative was identified as a potent inducer of Treg and Th1 immune response, resulting in strong IL-10 and moderate IFN-γ productions dose-dependently, while inducing no Th2 cytokine response. The immunomodulatory properties of this trivalent mannoside were further studied in vitro in allergen (Bet v)-stimulated human peripheral blood mononuclear cell cultures of birch pollen allergic subjects. Stimulation with birch pollen induced strong IL-4 and IL-5 responses, which could be suppressed by the trivalent acetylated mannobiose derivative. The IL-10 response was also suppressed, whereas the production of IFN-γ was strongly enhanced. The results suggest that the identified lead compound has suppressive effects on the Th2-type allergic inflammatory response and shows potential as a possible lead adjuvant for the specific immunotherapy of allergies.

Differential dose effect of fish oil on inflammation and adipose tissue gene expression in chronic kidney disease patients.

OBJECTIVE: The beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) in cardiovascular disease are partly attributed to their anti-inflammatory properties. Their potential effect on the adipose tissue of chronic kidney disease (CKD) patients has never been explored. METHODS: To determine the metabolic effect of supplementation with two different doses of fish oil (FO), 12 non-dialyzed patients with stage IV/V CKD were randomly allocated to receive 1.8 g or 3.6 g/d of ω-3 PUFA for 10 wk. Metabolic parameters, adipose tissue function, and gene expression were evaluated at baseline and 10 wk. RESULTS: Body weight, fat mass, energy intake, fasting glucose, and insulin were unchanged. The daily intake of 3.6 g of ω-3 PUFA resulted in decreased serum triacylglycerol and increased high-density lipoprotein cholesterol, whereas low-density lipoprotein cholesterol increased with 1.8 g of ω-3 PUFA. Serum adiponectin, leptin, C-reactive protein, and tumor necrosis factor-α were not modified in either group. Interleukin-6 levels tended to decrease with 1.8 g of ω-3 PUFA. Additionally, a subset of inflammation-related genes (CD68 and MMP9) was reduced in subcutaneous adipose tissue in this group. Adiponectin, leptin, and adipoR2 gene expression were upregulated with 3.6 g of ω-3 PUFA. CONCLUSIONS: A moderate dose of FO alters the gene expression profile of adipose tissue to a more antiinflammatory status. Higher doses of FO have a favorable effect on lipid profile and lead to the upregulation of adipokines gene expression suggesting a different dose response to ω-3 PUFA administration in patients with CKD.

Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Probiotics are defined as 'living micro-organisms that when administered in adequate amounts confer a health benefit to the host'. Different probiotic strains have been investigated for beneficial effects on allergic disorders. The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestlé culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR). SUBJECTS/METHODS: The study was a double-blinded, parallel, randomized placebo-controlled trial conducted during the peak of the pollen season. Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited. The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom questionnaires every week. Whole blood was collected at baseline (V1), 4 weeks (V2) and 8 weeks (V3) to measure immune parameters. RESULTS: Concentrations of Th-2 cytokines, secreted by stimulated blood lymphocytes, were significantly lower in the probiotic group compared with the placebo group at V3 (interleukin (IL)-5, P=0.016; IL-13, P=0.005). Total nasal symptom scores were significantly lower in the second month of the study (weeks 5-8) in the probiotic group compared with the placebo group (P=0.03). Also, percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 (P=0.02). CONCLUSIONS: Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure. These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy.

DHA-enriched fish oil targets B cell lipid microdomains and enhances ex vivo and in vivo B cell function.

DHA is a n-3 LCPUFA in fish oil that generally suppresses T lymphocyte function. However, the effect of fish oil on B cell function remains relatively understudied. Given the important role of B cells in gut immunity and increasing human fish oil supplementation, we sought to determine whether DFO leads to enhanced B cell activation in the SMAD-/- colitis-prone mouse model, similar to that observed with C57BL/6 mice. This study tested the hypothesis that DHA from fish oil is incorporated into the B cell membrane to alter lipid microdomain clustering and enhance B cell function. Purified, splenic B cells from DFO-fed mice displayed increased DHA levels and diminished GM1 microdomain clustering. DFO enhanced LPS-induced B cell secretion of IL-6 and TNF-α and increased CD40 expression ex vivo compared with CON. Despite increased MHCII expression in the unstimulated ex vivo B cells from DFO-fed mice, we observed no difference in ex vivo OVA-FITC uptake in B cells from DFO or CON mice. In vivo, DFO increased lymphoid tissue B cell populations and surface markers of activation compared with CON. Finally, we investigated whether these ex vivo and in vivo observations were consistent with systemic changes. Indeed, DFO-fed mice had significantly higher plasma IL-5, IL-13, and IL-9 (Th2-biasing cytokines) and cecal IgA compared with CON. These results support the hypothesis and an emerging concept that fish oil enhances B cell function in vivo.

Dietary mustard seeds (Sinapis alba Linn) suppress 1,2-dimethylhydrazine-induced immuno-imbalance and colonic carcinogenesis in rats.

In a Wistar rat model, prolonged supplementation of mustard seed (MS) to the diet significantly ameliorates the induction of colorectal carcinomas by 1,2-dimethylhydrazine (DMH). The expression of the splenocyte major histocompatibility complex class I (MHCI) was found significantly enhanced, whereas that of the major histocompatibility complex class II (MHCII) was significantly decreased. Compared to that of control animals, the proportion of spleenic B- and dendritic cells (DC) was amplified in the MS group. The expressions of MHCI, as well as that of MHCII, were increased in DC cells; whereas in B cells, MHCI expression was augmented but that of MHCII moderately decreased. The percentages of CD8+CD28+ and CD4+CD28+ cells were increased in the MS group, while the CD4+CD25+Foxp3+ subset was depressed. Plasma analysis showed that DMH-exposure induced amplified amounts of interleukin (IL)-4, IL-5, IL-10, and transforming growth factor-beta, whereas MS feeding counteracted this effect but enhanced IL-2, IL12p70, IL21, TNF-alpha, and interferon-gamma. In the SW480 colon adenocarcinoma cell-line, the cytotoxicity of spleenic T-cells from MS-fed animals was significantly increased. In the DMH-exposed rats, the expression of perforin in the spleenic T-cells was dramatically decreased, whereas MS abolished this depression. In summary, dietary MS suppresses DMH-induced immuno-imbalance as well as colon carcinogenesis in rats.

Progressive muscle relaxation therapy for atopic dermatitis: objective assessment of efficacy.

The aims of this study were to validate the efficacy of progressive muscle relaxation (PMR) in patients with atopic dermatitis and to evaluate the serological parameters that may serve as objective measures of the efficacy of PMR. A total of 25 patients with atopic dermatitis were randomly assigned to either a PMR group (n = 15) or a control group (n = 10). Serum levels of nerve growth, neuropeptide Y, and Th2 cytokines (IL-4, IL-5, and IL-13) were measured at baseline and after one month. At baseline, only anxiety was positively correlated with pruritus score (state anxiety: R = 0.496, p = 0.014; trait anxiety: R = 0.423, p = 0.04). Serum levels of neuropeptide Y were inversely related to the State-Trait Anxiety Inventory (STAI) (state anxiety: R = -0.475, p = 0.019; trait anxiety: R = -0.418, p = 0.042) and pruritus scores (R = -0.451, p = 0.035). After one month of PMR therapy, the degree of pruritus and loss of sleep was significantly decreased in the PMR group (p < 0.001), but not among controls. State anxiety scores showed significant improvement after treatment only in the PMR group (p = 0.005). There were no significant changes in the serological parameters in either group. Reductions in Eczema Area and Severity Index (EASI) scores were significant, but similar, in both groups. PMR may be a useful adjunctive modality for the management of atopic dermatitis through the reduction of anxiety. No change was found in biological parameters, but it was observed that neuropeptide Y may be related to high levels of anxiety in atopic dermatitis at baseline.

Antiasthmatic effects of Gleditsia sinensis in an ovalbumin-induced murine model of asthma.

This study evaluated the antiasthmatic effects of Gleditsia sinensis ethanolic extract (GSEE) and its underlying mechanisms, using an in vivo murine model of asthma. Female BALB/c mice were sensitized, challenged with ovalbumin, and then examined for asthmatic reactions. The results showed that GSEE exerted profound inhibitory effects on the accumulation of eosinophils in the airways and reduced the levels of interleukin (IL)-4 and IL-5 in bronchoalveolar lavage fluid (BALF) and immunoglobulin E (IgE) in BALF and plasma. Gleditsia sinensis ethanolic extract also suppressed the production of reactive oxygen species in BALF and inflammatory infiltration, in a dose-dependent manner, and it inhibited goblet-cell hyperplasia in lung tissue. Thus, GSEE shows antiasthmatic effects in a murine model of allergic asthma, which appeared to be mediated partially by the reduction of oxidative stress and airway inflammation. These results indicate that GSEE could be an effective novel therapeutic agent for the treatment of allergic asthma.

Plasma aluminum is a risk factor for oxidative stress and inflammation status in hemodialysis patients.

OBJECTIVES: The association between aluminum (Al), essential trace metals, oxidative stress, and inflammation status was evaluated in hemodialysis patients. DESIGN AND METHODS: Biochemical parameters in blood were determined in long-term hemodialysis patients (n=69) and age- and sex-matched healthy individuals (n=30). RESULTS: Compared with healthy subjects, patients had significantly higher concentrations of plasma Al. Elevated Al was negatively associated with the essential metals zinc, selenium, and iron. Al concentrations were strongly and positively correlated with contents of the oxidation products malondialdehyde and protein carbonyl. Inverse relationships were observed between Al concentrations and reduced concentrations of glutathione, ß-carotene, vitamin C, and vitamin E. Patients were also observed to have significantly increased production values of plasma high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-5. CONCLUSION: An increased plasma Al concentration is associated with disturbed concentrations of essential metals, increased oxidative stress, and increased inflammation status in hemodialysis patients.

[Effect of Ziyinqingsang decoction on interleukin-4 and -5 levels in peripheral blood mononuclear cells of children in acute stage of cough variant asthma].

OBJECTIVE: To observe the effect of Ziyinqingsang decoction on the levels of interleukin-4 (IL-4) and IL-5 in the peripheral blood mononuclear cells (PBMCs) in children with cough variant asthma (CVA) in the acute stage. METHODS: Thirty children with CVA in the acute stage were given Ziyinqingsang decoction for 2 weeks. The IL-4 and IL-5 levels in the PBMCs were determined using ELISA before and after the treatment, and the changes of the clinical symptoms were observed. RESULTS: The levels of IL-4 and IL-5 in the PBMCs was 89.69∓13.82 ng/l and 12.17∓0.43 ng/ml before the treatment, which were significantly reduced to 72.18∓14.89 ng/l and 5.81∓0.31 ng/ml after the treatment (P<0.05). The symptoms including coughing, pharyngodynia, and pharyngo-itch were all improved obviously (P<0.05). CONCLUSION: Ziyinqingsang decoction ameliorates the symptoms of CVA in the acute stage probably by decreasing the levels of IL-4 and IL-5 in the PBMCs of the children.

The effects of PG102, a water-soluble extract from Actinidia arguta, on serum total IgE levels: a double-blind, randomized, placebo-controlled exploratory clinical study.

BACKGROUND: Recent studies have reported that blocking IgE has a potentially beneficial role in the treatment of various allergic diseases. Previously, we found that PG102, a water-soluble extract prepared from the edible fruits of Actinidia arguta, can effectively reduce IgE levels using murine models. AIMS: To evaluate the efficacy of PG102 at lowering levels of total IgE in asymptomatic subjects with atopy. METHODS: A total of 90 asymptomatic subjects with atopy were randomized equally to a PG102 group or a placebo control group and treated for 8 weeks in a double-blind manner. Total serum IgE, eosinophilic cation protein (ECP), eotaxin, thymus, and activation-regulated chemokine (TARC), IL-4, IL-5, and IL-13 levels were measured. Eosinophil counts were determined before and after treatment, and results were compared. In addition, possible adverse reactions were thoroughly checked in this first human trial. RESULTS: Levels of total IgE significantly increased in the control group but showed no change in the PG102 group, and change differences between the control and PG102 groups were significant (+12.9%, vs.-5.7%, p = 0.015). Levels of ECP and eotaxin and eosinophil counts produced similar results. However, the other variables showed no significant changes after treatment. CONCLUSION: In this exploratory clinical trial, it was found that 8 weeks of treatment with PG102 effectively reduced the levels of total IgE in apparently asymptomatic subjects with atopy.

Production of interleukin-5, -10 and interferon-γ in cord blood is strongly associated with the season of birth.

BACKGROUND: The effect of labour and different labour-related factors on the cord blood (CB) cell cytokine production is still relatively unknown. OBJECTIVE: To study the relationships between the production of IL-5, IL-10 and IFN-γ in CB samples and maternal, early neonatal and birth-related factors. METHODS: Whole-blood samples were collected after birth (n=423) and they were stimulated for 24 and 48 h with a combination of phorbol ester and ionomycin. Production of IL-5, IL-10 and IFN-γ was determined using ELISA. Maternal, early neonatal and birth-related variables were recorded prospectively during pregnancy, and during and after delivery. RESULTS: After multivariable adjustment for confounders, the strongest predictor of IL-5, IL-10 and IFN-γ production in CB cell samples was the season of birth. Children born in the spring had significantly lower cytokine responses compared with those born in the fall. IL-5 production was inversely associated with female gender of the child and maternal smoking. If corrections for white blood cell (WBC) counts were not performed, IL-5 production was also significantly associated with the mode of delivery. Respectively, the production of IL-10 and IFN-γ was inversely associated with prostaglandin induction before birth. CONCLUSION: Environmental exposure to pollen and ultraviolet irradiation during gestation may have an effect on the cytokine profile of the offspring in CB because children born in the spring or winter showed the lowest IL-5, IL-10 and IFN-γ responses. The production of IL-10 and IFN-γ was also inversely associated with prostaglandin labour induction before birth. Other labour-related factors were not significantly associated with production of IL-5, IL-10 and IFN-γ after WBC count correction.

The role of T-lymphocyte subsets and interleukin-5 blood levels among Indian subjects with autoimmune thyroid disease.

OBJECTIVE: Autoimmune Thyroid Disease (AITD) results from an interaction of exogenous and endogenous factors in a genetically predisposed individual. AITD is being increasingly reported among the Indian population. Lymphocyte subsets and levels of interleukin-5 (IL- 5) were studied in the peripheral blood of patients with AITD. DESIGN: Subjects diagnosed with either hyperthyroidism due to Graves' Disease (GD) or with primary hypothyroidism due to Hashimoto's Thyroiditis (HT) were consecutively recruited. Euthyroid controls were also recruited for comparison. Lymphocyte subsets (CD4 and CD8 counts, CD4/CD8 ratio) were evaluated by flow cytometry and IL-5 levels were determined by the sandwich ELISA method. RESULTS: Nineteen subjects with GD, 16 subjects with HT and 10 controls were studied. CD4/CD8 ratios were found to be significantly lower only in subjects with HT compared to controls. Serum IL-5 values were significantly higher in both GD and HT in comparison to controls. CONCLUSIONS: The study found increased levels of IL-5 and reduction in ratios of CD4/CD8 lymphocytes in the peripheral blood of patients with HT, but only IL-5 was increased in GD. High levels of IL-5 could have resulted in the high titres of antithyroid antibodies and may therefore be considered to play a more significant role than peripheral lymphocytes in the pathogenesis of AITD in the Indian population.

Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats.

PURPOSE: The present study compared the ability of different berry types to prevent chemically-induced tumorigenesis in the rat esophagus. We also determined if berries influence the levels of inflammatory cytokines in the serum of carcinogen-treated rats. METHODS: Rats were treated with the carcinogen N-nitrosomethylbenzylamine (NMBA) for 5 weeks, then placed on diets containing 5% of either black or red raspberries, strawberries, blueberries, noni, açaí or wolfberry until the end of the study. The effects of the berries on tumor incidence, multiplicity and size were determined, as well as their effects on the levels of selected inflammatory cytokines in serum. RESULTS: All berry types were about equally effective in inhibiting NMBA-induced tumorigenesis in the rat esophagus. They also reduced the levels of the serum cytokines, interleukin 5 (IL-5) and GRO/KC, the rat homologue for human interleukin-8 (IL-8), and this was associated with increased serum antioxidant capacity. CONCLUSIONS: Seven berry types were about equally capable of inhibiting tumor progression in the rat esophagus in spite of known differences in levels of anthocyanins and ellagitannins. Serum levels of IL-5 and GRO/KC (IL-8) may be predictive of the inhibitory effect of chemopreventive agents on rat esophageal carcinogenesis.