Bi-Fong Lin

Tamoxifen alleviates disease severity and decreases double negative T cells in autoimmune MRL-lpr/lpr mice

Previous study suggested that MRL‐lpr/lpr mice treated with tamoxifen (TAM) had less severe proteinuria, reduced serum titre of anti‐dsDNA autoantibodies and an increased survival rate. To investigate further the regulatory mechanisms of TAM on MRL‐lpr/lpr female mice, a total dose of 200 µg per mice (5·5 mg/kg) was given every 2 weeks subcutaneously, while the control mice were injected with oil only. After being treated with TAM four times, the mice were killed and cellular functions were evaluated. The TAM‐treated groups had smaller sized spleen and lymph nodes. Flow cytometric analysis of splenocytes had a significantly lower percentage of cell number of T cells and double negative T cells (CD4– CD8– T cells). There was no difference in cytokine production (interleukin (IL)‐2, IL‐4, IL‐5, IL‐10 and interferon‐γ (IFN‐γ)) from splenocytes stimulated with concanavalin A (Con A) or cytokines (IL‐6) secreted by peritoneal exudate cells when stimulated with lipopolysaccharide (LPS). However, IL‐2 from lymph node cells was significantly higher on TAM‐treated mice. Finally, splenocytes or purified T cells stimulated with anti‐CD3 antibody plus cross‐linking immunoglobulin G (IgG) of the TAM‐treated group had higher 3H‐incorporation of proliferation assay compared with that of control groups. In vitro study further demonstrated that IL‐2‐activated proliferation of lymph node double negative (DN) T cells can be inhibited by TAM treatment in a dose‐dependent manner. Our finding demonstrated that TAM may potentially influence T cells and modulate the immune function, which offers a novel approach to explore the feasibility of hormone therapy for autoimmune diseases.

The effects of vitamin E supplementation on autoimmune-prone New Zealand black × New Zealand white F1 mice fed an oxidised oil diet

The purpose of the present study was to investigate the effect of vitamin E supplementation on autoimmune disease in New Zealand blackxNew Zealand white F1 (NZB/W F1) female mice fed an oxidised oil diet. First, 5-month-old mice were fed an AIN-76 diet containing either 150 g fresh soyabean oil/kg (15S), 50 g fresh soyabean oil/kg + 100 g oxidised frying oil/kg (5S10F) or 5S10F supplemented with all-rac-alpha-tocopheryl acetate at 275 mg/kg diet level (5S10F5E) or 550 mg/kg (5S10F10E), respectively, in experiment 1. The results showed that mice fed the 5S10F10E diet had a lower anti-double-stranded DNA IgG antibody level and a longer lifespan than those fed the 15S and 5S10F diets. Therefore, the 5S10F and 5S10F10E treatments were repeated in experiment 2 for further analysis. The results showed that vitamin E supplementation in the oxidised oil significantly decreased thiobarbituric acid-reactive substance values in the kidney and spleen of NZB/W F1 mice. Interferon-gamma and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed the 5S10F10E diet, whereas the secretion of IL-2 and IL-10 was not affected. The percentage of T-cells was significantly higher and that of MHC class II-bearing cells was lower in the spleens of the 5S10F10E group. The 5S10F10E group had a significantly higher linoleic acid (18 : 2n-6) composition than the 5S10F diet group. Therefore, vitamin E supplementation in oxidised oil might decrease oxidative stress, anti-double-stranded DNA IgG antibody, regulate cytokines and lymphocyte subsets, and subsequently alleviate the severity of autoimmune disease such as systemic lupus erythematosus under oxidative stress.

Dietary oxidized oil influences the levels of type 2 T-helper cell-related antibody and inflammatory mediators in mice

The aim of this present study was to investigate the effect of amount and degree of oxidation of dietary oil on type 2 T-helper cell (TH)-related immune responses. Four groups of BALB/c mice were fed either 50 g soyabean oil/kg (50-S), 50 g oxidized oil/kg (50-O), 150 g soyabean oil/kg (150-S) or 150 g oxidized oil/kg (150-O). After 14 weeks consuming the experimental diets, the mice were immunized with ovalbumin (OVA) plus Al and antigen-specific immunoglobulin (Ig)E, IgG1 and IgG2a, inflammatory mediators such as prostaglandin (PG) E2 and leukotriene (LT)B4 were determined. Higher hepatic microsomal cytochrome P450 was noted in mice fed 150 g oxidized oil/kg compared with those of other groups. OVA-specific IgG1 and IgE were higher in mice fed 150 g oxidized oil/kg compared with those of the other groups. The data suggested the interleukin (IL)-4: interferon (IFN)-gamma ratio was higher in mice fed 50 g dietary oxidized oil/kg compared with that of the 50-S group. The IL-5:IFN-gamma ratios were higher in the 150-S and 150-O groups than in the 50-S and 50-O groups. PGE2 and LTB4 produced by macrophages stimulated by lipopolysaccharide were highest in mice in the 150 g oxidized oil/kg group. The data suggested that an increased intake of oxidized oil might exert an unfavourable effect on the TH2 response involved in allergic disease.

Different dietary fats influence serum and tissue lipids and anti-cardiolipin antibody levels in autoimmune-prone NZB/W F1 mice

To investigate the influence of different dietary fats on lipids and anti-cardiolipin antibody levels, autoimmune NZB/W F1 mice were fed on diets containing 200 g dietary fat as palm oil, lard-soyabean oil (1:1, w/w), soyabean oil, rapeseed oil or fish oil/kg. In addition, each dietary fat group was divided into an early-feeding group with feeding from 2 months of age, and a late-feeding group with feeding from 5 months of age. Serum levels of triacylglycerol, phospholipid, cholesterol and anti-cardiolipin antibody were measured at regular intervals, and mice were killed at the age of 7 months for analysis of hepatic lipid and fatty acids. The results showed that hepatic triacylglycerol and cholesterol contents were lower in mice fed on fish oil than in those fed on palm oil. In contrast, hepatic phospholipid content was higher in mice of the fish oil group than in those of the other four dietary fat groups. Composition profiles for both hepatic and renal oleic acid (18: 1n-9), linoleic acid (18: 2n-6) and eicosapentaenoic acid (20: 5n-3) were similar to those of the dietary fats in mice of both early-feeding and late-feeding groups. Fish oil intake decreased arachidonic acid (20: 4n-6) concentration in kidney tissue but not in liver tissue. Serum triacylglycerol, cholesterol and phospholipid levels were lower in mice fed on fish oil than in those fed on palm oil. Immunoglobulin (Ig) M anti-cardiolipin antibody was lower for the fish oil group than for the other groups. The IgG anti-cardiolipin antibody level was significantly lower in mice fed on fish oil compared with that of the palm oil group only in the early-feeding group. There was a positive correlation between serum IgM anti-cardiolipin antibody and phospholipid levels (early-feeding group r 0.902, P < 0.05; late-feeding group r 0.894, P < 0.05). These findings suggest dietary fish oil may affect both lipid levels and anti-cardiolipin antibody, contributing to alleviation of the autoimmune process in autoimmune-prone NZB x NZW F1 mice.

Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities

This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+ T cells cultures also confirmed that Gt-TRE (5 ~ 50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.

Traditional Herbal Medicine and Allergic Asthma

The frequency of allergic diseases such as asthma and allergic rhinitis has increased rapidly during the past decade; however, the exact mechanisms have still not been established. Both air pollution and change of diet habit have been thought to play an important role in increasing prevalence of atopic diseases. Atopic diseases were mediated predominantly by type 2 T helper- (Th2-) mediated activity including allergen-specific IgE antibody and eosinophils. Allergic asthma is a chronic disease with the characteristics of immune response mediated by type 2 T helper- (Th2-) related cytokines and IgE antibody. Allergic airway inflammation has been characterized by the infiltration of Th2 cells and eosinophils, subsequently followed by the bronchial constriction and mucus secretion. Conventional treatments for allergic asthma include steroids, leukotriene antagonists, bronchodilators, and most recent anti-IgE antibody. All these drugs are still with certain shortcomings such as side effects, effectiveness, and cost. It has become more and more important to develop novel therapeutic approaches for the treatment of allergic asthma. Complementary medical approaches such Chinese herb medication and acupuncture have been suggested to play a role in the immune regulation of diseases [1]. More studies have focused on exploring the possibility of these complementary therapeutic approaches for the treatment of immunological diseases [2]. All these complimentary therapeutic approaches have been regarded as having less side effects and being used as the adjuvant therapy for the diseases [3]. Furthermore, many researchers also aim to identify the active components of herb medicine for the purification and development of drugs. In this special issue, we have five articles including the survey of traditional Chinese medicine application for the treatment of allergic asthma and also the study on the traditional Tianjiu therapy for the treatment of asthmatic patients. Furthermore, three articles on studying the active components of herb medicine have been included in the issue. S.-I. Lin et al. analyzed the use of Chinese traditional medicine for the treatment of allergic asthma in Taiwan. They collected 20,800 newly diagnosed asthmatic children and found out 20% of them actually used traditional Chinese medicine as the treatment of their asthma. In addition, they also analyzed the most frequent used herbal medicine for allergic asthma in the article. A variety of components purified from medicinal herbs have been found to exert the immune modulatory effect on many diseases [4]. Among the components, polyphenols, triterpenoids, and polysaccharides are found to be the most effective in the anti-inflammatory or immune modulation of the diseases. M.-L. Chen et al. have identified both triterpenoids and polysaccharide portion for the treatment of allergic diseases. The results showed that triterpenoids portion of Ganoderma tsugae exerted anti-inflammatory activity and polysaccharide portion had the immune stimulatory effect instead. C.-M. Ku and J.-Y. Lin also identified an active component of farnesol, a sesquiterpene alcohol, exerting anti-inflammatory activity and alleviating airway inflammation in murine model of asthma. M.-L. Chen et al. also identified ethanol extract of Perilla frutescens which also exerted anti-inflammatory activity and also alleviated allergic airway inflammation. Finally, L. Zhu et al. studied the effect of Tianjiu therapy in Sanfu Days for the treatment of asthmatic children. The results suggested that Tianjiu therapy could decrease the dose of bronchodilator during the asthma attack. However, the symptoms of allergic asthma did not show significant improvement after treatment. More studies are needed for the application of Tianjiu therapy for the treatment of allergic asthma in the future. The prevalence of clinical immunological diseases such as autoimmune diseases and allergic diseases is increasing in recent years. More and more efforts have been dedicated to develop novel therapeutic approaches for the treatment of these immune-mediated diseases. Complimentary medicine such as herb drugs or acupuncture has been suggested to be useful for the treatment of a variety of clinical immunological diseases [5]. Many of these herb medicinal components have been found to exert anti-inflammatory activity and modulation of immune response. Although more studies are needed to identify the novel compounds and the treatment, it might still be the future target for the novel therapeutic development. Particularly, these herb medicinal drugs are noted with fewer side effects, which might also be useful for possible adjuvant therapy. Bi-Fong Lin Bor-Luen Chiang Yan Ma Jin-Yuarn Lin Miaw-Ling Chen