Coix Seed Consumption Affects the Gut Microbiota and the Peripheral Lymphocyte Subset Profiles of Healthy Male Adults.

A systematic examination of the effects of traditional herbal medicines including their mechanisms could allow for their effective use and provide opportunities to develop new medicines. Coix seed has been suggested to promote spontaneous regression of viral skin infection. Purified oil from coix seed has also been suggested to increase the peripheral CD4+ lymphocytes. We, herein, attempt to shed more light on the way through which coix seed affects the human systemic immune function by hypothesizing that a central role to these changes could be played through changes in the gut microbiota. To that end, healthy adult males (n = 19) were divided into two groups; 11 of them consumed cooked coix seed (160 g per day) for 7 days (intervention), while the other eight were given no intervention. One week of coix seed consumption lead to an increase of the intestinal Faecalibacterium abundance and of the abundance (as % presence of overall peripheral lymphocytes) of CD3+CD8+ cells, CD4+ cells, CD4+CD25+ cells, and naïve/memory T cell ratio. As the relationship of microbiota and skin infection has not been clarified, our findings could provide a clue to a mechanism through which coix seed could promote the spontaneous regression of viral skin infections.

Ruxolitinib Cream Has Dual Efficacy on Pruritus and Inflammation in Experimental Dermatitis.

The goal of this study was to elucidate the anti-pruritic and anti-inflammatory efficacy of ruxolitinib cream in experimentally-induced dermatitis. Atopic dermatitis (AD), the most common chronic relapsing inflammatory skin disease, significantly impairs patients' quality of life, with pruritus being a common complaint. The sensation of itch results from the interplay between epidermal barrier dysfunction, upregulated immune signaling and the activation of the central nervous system. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a central role in pro-inflammatory cytokine signaling in AD. Ruxolitinib cream is a potent and selective JAK1/2 inhibitor currently undergoing clinical evaluation in adults with mild-to-moderate AD (NCT03745638, NCT03920852 and NCT03745651). The efficacy of ruxolitinib cream was tested in murine models of acute and chronic dermatitis and was also characterized in an ex vivo human skin dermatitis model. Ruxolitinib cream was highly effective at ameliorating disease symptoms in multiple murine dermatitis models through downregulation of T helper (Th)2-driven inflammation, resulting in reduced skin thickening and decreased itch. Pathway analysis of mouse ear tissue and human skin explants underscored the role for ruxolitinib in ameliorating inflammation and reducing itch via modulation of the JAK-STAT pathway. Together, the data offer a strong rationale for the use of ruxolitinib cream as a potent therapeutic agent for the clinical management of atopic dermatitis.

Hawthorn (Crataegus monogyna) Phenolic Extract Modulates Lymphocyte Subsets and Humoral Immune Response in Mice.

This study investigated the effect of hawthorn (Crataegus monogyna) phenolic extract on lymphocyte subsets in the lymphoid organs in nonimmunized mice and on humoral immune response in sheep red blood cell-immunized mice. Hawthorn phenolic extract (50, 100, 200 mg/kg) was administered orally five or ten times. Sheep red blood cells were injected 24 h after administration of the last extract dose. The lymphocyte subsets were assessed 24 and 72 h after the last dose. Humoral immune response was determined 4 and 7 days after immunization. Five doses of the extract decreased the percentage of CD4-CD8- and CD4+ thymocytes but elevated the percentage of CD4+CD8+ and CD8+ thymic cells. The extract increased the total number, percentage, and absolute count of T and B splenocytes. When administered five times, it lowered the percentage of T lymphocytes, but boosted the population of B lymphocytes of mesenteric lymph nodes (after 24 h). However, a rise in the population of T lymphocytes was observed 72 h after five and ten doses. The extract administered ten times elevated the number of plaque-forming cells and total anti-sheep red blood cell hemagglutinin titer but reduced the 2-ME-resistant antibody titer (day 7). At the same time, five doses of the extract increased antibody titers. Considering its impact on lymphocyte subsets and humoral immune response, hawthorn extract may be used as an immunomodulator.

Leptin and EGF Supplementation Enhance the Immune System Maturation in Preterm Suckling Rats.

In preterm newborns the immaturity of the immune system is remarkable, with reduced innate and adaptive immune responses. Many bioactive compounds in breast milk, such as growth factors and adipokines, contribute to the immune system's maturation in early life. However, studies on the immunoregulatory activity in preterm neonates are practically nonexistent. The aim of the present study was to determine whether a nutritional supplementation in early life with leptin or epidermal growth factor (EGF) was able to promote the maturation of the systemic and intestinal immune system in preterm conditions. For this purpose, premature rats were daily supplemented by oral gavage with leptin or EGF. Term and Preterm groups receiving vehicle were used as controls. Preterm rats showed deficiencies compared to full-term ones, such as lower body weights, erythrocyte counts, plasma IgG and IgM concentrations and B cell percentages, and higher values of Th and Tc TCRαß+ cells in mesenteric lymph nodes, and intestinal permeability, among others. However, leptin and EGF supplementation were able to revert some of these deficiencies and to improve the premature immune system's development. These results suggest that leptin and EGF are involved in enhancing the maturation of the systemic and intestinal immune system in preterm conditions.

Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism.

The heterogeneity of asthma involves complex pathogenesis leading to confusion regarding the choice of therapeutic strategy. In the clinic, asthma is commonly classified as having either eosinophilic asthma (EA) or non-eosinophilic asthma (NEA) phenotypes. Microbiota colonizing in airways has been demonstrated to induce distinct phenotypes of asthma and the resistance to steroids. Rhodiola wallichiana var. cholaensis (RWC) has the potential to alleviate asthmatic inflammation according to recent studies, but its pharmacological mechanisms remain unclarified. In our study, murine asthmatic phenotypes were established and treated with RWC and/or dexamethasone (DEX). Combined treatment with RWC and DEX could improve spirometry and airway hyperresponsiveness (AHR) in asthmatic phenotypes, alleviate steroid resistance in NEA, and reduce the inflammatory infiltration of the both phenotypes. The combined treatment increased Th1, regulated the imbalance of Th2/Th1, and decreased the related cytokines in EA. As for NEA, the combined treatment reduced Th17 and promoted the accumulation of regulatory T cells (Tregs) in lung. A microbiome study based on 16S rDNA sequencing technique revealed the significantly changed structure of the lower airway microbiota after combined treatment in NEA, with 4 distinct genera and 2 species identified. OPLS-DA models of metabolomics analysis based on UPLC-Q/TOF-MS technique identified 34 differentiated metabolites and 8 perturbed metabolic pathways. A joint multiomics study predicted that the colonized microbiota in airways might be associated with susceptibility of asthma and steroid resistance, which involved systematic and pulmonary metabolic perturbation. In summary, the pharmacological network of RWC included the complicated interaction mechanisms of immune regulation, microbiota change, and metabolic perturbation.

Dihydroartemisinin Regulates the Th/Treg Balance by Inducing Activated CD4+ T cell Apoptosis via Heme Oxygenase-1 Induction in Mouse Models of Inflammatory Bowel Disease.

Dihydroartemisinin (DHA) is a derivative of the herb Artemisia annua L. that has prominent immunomodulatory activity; however, its underlying mechanism remains elusive. Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition characterized as an autoimmune disorder that includes dysfunctions in the T helper (Th)/T regulatory cell (Treg) balance, which normally plays pivotal roles in immune homeostasis. The aim of this study was to explore the potential of DHA to ameliorate IBD by restoring the Th/Treg cell balance. To this end, we established mouse models of colitis induced by oxazolone (OXA) and 2,4,6-trinitro-benzene sulfonic acid (TNBS). We then treated mice with DHA at 4, 8, or 16 mg/kg/day. DHA treatment ameliorated colitis signs and reduced lymphocyte infiltration and tissue fibrosis. Moreover, DHA decreased the numbers of Th1 and Th17 cells and Th9 and Th22 cells in TNBS- or OXA-induced colitis, respectively, and increased Tregs in both models. DHA (0.8 mg/mL) also inhibited activated CD4+ T lymphocytes, which was accompanied by apoptosis induction. Moreover, it promoted heme oxygenase-1 (HO-1) production in vitro and in vivo, concomitant with CD4+ T cell apoptosis and restoration of the Th/Treg balance, and these effects were blocked by treatment with the HO-1 inhibitor Sn-protoporphyrin IX. Overall, these results suggest that DHA is a novel and valuable candidate for IBD therapy or Th/Treg immunoregulation.

Effect of Neoadjuvant and Adjuvant Therapy of Experimental Breast Cancer on the Structure of Mesenteric Lymph Nodes.

The morphometric analysis of mesenteric lymph nodes was carried out in female Wistar rats with chemically induced breast cancer. In control rats with untreated breast cancer, the volume of the system of sinuses increased in parallel with the appearance of morphological signs of suppression of cell-mediated immunity, inhibition of humoral immunity, and macrophage reaction. Against the background of chemotherapy, we observed a decrease in the volume of paracortex and lymphoid nodules, suppression of proliferative activity of lymphoid cells in paracortical and B-cell zone, and a decrease in macrophage content. After resection of breast cancer followed by chemotherapy course, lymph transport activation, widening of the paracortex, enhanced proliferative activity of cells in the paracortex and B-cell zone, and reduced volumes of lymphoid nodules with and without germinal centers and medullary substance were revealed in comparison with rats subjected neoadjuvant chemotherapy.

Antiviral effects of Ma Huang Tang against H1N1 influenza virus infection in vitro and in an ICR pneumonia mouse model.

Ma Huang Tang (MHT), a classical Chinese herbal decoction which has been used in clinic for thousands of years, was very effective in treating the upper respiratory tract infection. But its activity against influenza virus A, the anti-inflammatory effect and the underlying mechanisms have been poorly investigated in previous researches. In this study, the antiviral efficacy of MHT directly inhibiting influenza virus A was investigated in vitro in MDCK cells. In an ICR pneumonia mouse model infected with influenza virus A PR/8/34, MHT (8, 4 and 2 g/kg) were oral administrated for 7 days after viral challenge, to evaluate the effect of MHT on ameliorating viral pneumonia and decipher the underlying mechanisms. The in vitro results showed that MHT possessed antiviral activity with low toxicity. The in vivo assays showed that MHT (8 and 4 g/kg) significantly attenuated lung histopathological changes, decreased lung index, interleukin (IL)-4,5, tumor necrosis factor alpha (TNF-α), CD3+, CD8+ T cell levels, increased IL-2, gamma interferon (IFN-γ), CD4+ T cell levels and CD4+/CD8+ ratio, inhibited toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF6) protein levels. All these results demonstrate that MHT can strikingly ameliorate influenza virus A pneumonia in mice, which is associated with the regulating effect of MHT in the imbalance of body's immune function and the MyD88-dependent signaling pathway of TLR4.

Effects of iridoid-anthocyanin extract of Cornus mas L. on hematological parameters, population and proliferation of lymphocytes during experimental infection of mice with Trichinella spiralis.

The influence of iridoid-anthocyanin aqueous extract of cornelian cherry fruits (CM) on hematological parameters, lymphocyte subsets and proliferation during Trichinella spiralis infection in mice was investigated. CM (100 mg/kg) was administered orally to T. spiralis-infected mice six times within a period encompassing three days prior to the infection and three days after the infection (dai). CM increased the percentage of CD3+, CD4+ cells and CD4+/CD8+ ratio and decreased total count of CD8+ and CD19+ splenocytes (5th dai). An increase in total count of CD4+, CD3+, CD19+ splenocytes was observed (21st dai). CM elevated the percentage of CD4+ cells (7th dai) and CD4+/CD8+ ratio (21st dai) in MLN. CM increased (14th dai) and then reduced (21st dai) the percentage of CD8+ MLN lymphocytes and decreased total count of MLN CD8+ cells (21st dai) and B cells (14th dai). An activation of lymphocyte proliferation in spleen and simultaneous decrease in MLN on 5th dai was observed. An increase in red blood cells parameters (5th dai) and in leukocyte count (7th dai) was found. A rise in platelet count was noticed both on 5th and 7th dai. Moreover, the number of adult T. spiralis on 5th dai in mice receiving CM extract was lower than in the control mice. These results suggested that iridoid-anthocyanin aqueous extract of CM stimulated murine immune response during T. spiralis infection.

The Effect of Safranal on Th1/Th2 Cytokine Balance.

BACKGROUND: Several biological and medical benefits of Saffron, Crocus sativus (Iridaceae), have been demonstrated. However, mechanisms of actions for purified constituents are greatly unknown. OBJECTIVE: To examine the effects of Safranal, a main constituent of Saffron stigma, on cell viability and cytokine profile of peripheral blood mononuclear cells (PBMC) were examined. METHODS: Effects of Safranal at 0.1, 0.5 and 1 mM concentrations were evaluated on cell viability and production of interleukin 4 (IL-4), IL-10 and interferon-γ (IFN-γ) from non-stimulated and phytohemagglutinin (PHA) stimulated PBMCs, compared to 0.1 mM dexamethasone and saline. RESULTS: In stimulated cells, different concentrations of Safranal caused significant decrease of lymphocytes viability (p<0.001 for all concentrations). All concentrations of Safranal inhibited IFN-γ and IL-10 secretion in stimulated cells (p<0.01). In addition, higher concentrations of Safranal significantly decreased cell viability of non-stimulated PBMCs (p<0.001). The effect of 1 mM Safranal on IL-4 secretion was less than dexamethasone (p<0.05). Safranal showed a stimulatory effect on IFN-γ secretion in non-stimulated cells. The IFN-γ/IL-4 ratio at the presence of two higher Safranal concentrations both in non-stimulated and stimulated cells were significantly higher than those of control and PHA stimulated groups, respectively (p<0.05). CONCLUSION: The IFN-γ/IL-4 ratio increases in the presence of Safranal which indicates an effect on Th1/Th2 balance. Therefore, Safranal may have therapeutic effects in inflammatory diseases associated with Th1/Th2 imbalance.

Effects of Shen-Fu Injection () on apoptosis of regulatory T lymphocytes in spleen during post-resuscitation immune dysfunction in a porcine model of cardiac arrest.

OBJECTIVE: To investigate whether Shen-Fu Injection (, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen. METHODS: After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine (EP) group, and saline (SA) group (8 in each group), which received central venous injection of SFI (1.0 mL/kg), EP (0.02 mg/kg) and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated (sham) group (n=6). After successful return of spontaneous circulation (ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the mRNA expression of forkhead/winged helix transcription factor (Foxp3) of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 mRNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group (P<0.05 or P<0.01). Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 mRNA expression, IFN-γ and IFN-γ/IL-4 (P<0.05). CONCLUSIONS: SFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.

Differential Effects of Viscum album Preparations on the Maturation and Activation of Human Dendritic Cells and CD4⁺ T Cell Responses.

Extracts of Viscum album (VA); a semi-parasitic plant, are frequently used in the complementary therapy of cancer and other immunological disorders. Various reports show that VA modulates immune system and exerts immune-adjuvant activities that might influence tumor regression. Currently, several therapeutic preparations of VA are available and hence an insight into the mechanisms of action of different VA preparations is necessary. In the present study, we performed a comparative study of five different preparations of VA on maturation and activation of human dendritic cells (DCs) and ensuing CD4⁺ T cell responses. Monocyte-derived human DCs were treated with VA Qu Spez, VA Qu Frf, VA M Spez, VA P and VA A. Among the five VA preparations tested VA Qu Spez, a fermented extract with a high level of lectins, significantly induced DC maturation markers CD83, CD40, HLA-DR and CD86, and secretion of pro-inflammatory cytokines such as IL-6, IL-8, IL-12 and TNF-α. Furthermore, analysis of T cell cytokines in DC-T cell co-culture revealed that VA Qu Spez significantly stimulated IFN-γ secretion without modulating regulatory T cells and other CD4⁺ T cytokines IL-4, IL-13 and IL-17A. Our study thus delineates differential effects of VA preparations on DC maturation; function and T cell responses.

Differential effects of Rhodiola rosea on regulatory T cell differentiation and interferon­Î³ production in vitro and in vivo.

Rhodiola rosea (R. rosea), a type of adaptogen, has been previously reported to exhibit immunostimulating activity in rodents and in human peripheral blood mononuclear cells (PBMCs) in vitro. To examine the effect of R. rosea on T cells under simulated microgravity, spaceflight analogs of human head­down bed rest (HDBR) at ­6˚ and murine hind limb unloading (HU) were used. A decrease in the levels of interferon­Î³ (IFN­Î³) and interleukin­17 (IL­17) and an increase in regulatory T (Treg) cells were observed in the placebo group following HDBR. The R. rosea treated HBDR group demonstrated further decreased IFN­Î³ production, however, R. rosea exhibited no effect on the ratio of circulating Tregs or Treg cell differentiation. By contrast, the treatment of R. rosea on human T cells in vitro did not alter IFN­Î³ secretion, however, Treg differentiation was significantly reduced. An R. rosea­induced upregulation of hypoxia­inducible factor 1α (HIF­1α) contributed to the suppression of Treg differentiation in vitro. Differences in the effect of R. rosea in vitro and in vivo were also observed using a mouse model of microgravity. The results of the current study suggest that R. rosea has differential modulatory effects on T cells in vivo and in vitro and care should be taken when evaluating the effects of R. rosea on the immune system.

Erythronium japonicum attenuates histopathological lung abnormalities in a mouse model of ovalbumin-induced asthma.

Asthma is a chronic lung condition that can induce mucus hypersecretion and pulmonary obstruction and may even cause death, particularly in children and older individuals. Erythronium japonicum (E. japonicum) is a traditional herb used in Korea and East Asian countries that has been found to exert free radical scavenging activity and anti-proliferative effects in human colorectal carcinoma cells. In the present study, we evaluated the anti-asthmatic effects of an extract of E. japonicum in a mouse model of ovalbumin (OVA)­induced asthma. Female BALB/c mice were sensitized with an intraperitoneal injection of OVA and aluminum hydroxide hydrate on days 1 and 8 and then received the following treatments on days 21 to 25: i) control (no treatment), ii) sterilized tap water (given orally), iii) 1 mg/kg/day dexamethasone (administered orally), iv) 60 mg/kg/day E. japonicum extract, and v) 600 mg/kg/day E. japonicum extract. On the same days, all the mice except those in the control group were challenged 1 h later with nebulized 5% OVA for 30 min. We found that treatment with E. japonicum extract suppressed the OVA-induced increase in the number of white blood cells and decreased the IgE level in the bronchoalveolar lavage fluid samples obtained from the mice. Histopathological analysis of the lung tissues revealed that E. japonicum attenuated the asthma-related morphological changes in the mouse lung tissue, including the increased secretion of mucus in the bronchioles, eosinophil infiltration around the bronchioles and vessels, and goblet cell and epithelial cell hyperplasia. Immunohistochemical analysis revealed that treatment with E. japonicum extract suppressed the OVA-induced proliferation of T helper cells (CD4+) and B cells (CD19+) in the mouse lung tissue. Furthermore, treatment with E. japonicum extract modulated the expression of both T helper 2 cell-related factors [GATA binding protein 3 (GATA-3), tumor necrosis factor-α (TNF­α), interleukin (IL)-4, IL-5, IL-6 and IL-13], as well as that of T helper 1 cell-related factors [(interferon-γ (IFN-γ), IL-12p35 and IL-12p40]. These findings suggest that E. japonicum may potentially be used as an anti-asthmatic treatment.

The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain.

Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight, prolonged average life span and ameliorated spatial memory impairment in 12- and 24-month-old senescence accelerated mouse resistant 1 (SAMR1) strain. And these anti-aging effects of LW-AFC were more excellent than melatonin. The administration of LW-AFC enhanced ConA- and LPS-induced splenocyte proliferation in aged SAMR1 mice. The treatment of LW-AFC not only reversed the decreased the proportions of helper T cells, suppressor T cells and B cells, the increased regulatory T cells in the peripheral blood of old SAMR1 mice, but also could modulate the abnormal secretion of IL-1ß, IL-2, IL-6, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α, TNF-ß, RANTES, eotaxin, MCP-1, IL-4, IL-5, IL-10 and G-CSF. These data indicated that LW-AFC reversed the immunosenescence status by restoring immunodeficiency and decreasing chronic inflammation and suggested LW-AFC may be an effective anti-aging agent.

Chrono- and Immunocorrection of Inflammatory Disorders of Internal Reproductive Organs in Women of Reproductive Age.

We compared the effectiveness of immunomodulators used in the treatment of patients with chronic salpingitis and oophoritis with or without changes in succinate dehydrogenase (SDH) activity in blood lymphocytes at incubation with the drug. Diurnal variations in individual reaction of SDH in blood lymphocytes to thymalin or ridostin were revealed. In the groups of women receiving ridostin or thymalin during the reaction of lymphocyte SDH to it, improvement of clinical laboratory and immunological parameters was observed in the majority of the patients and no effect was found in a lesser group of patients than in the groups treated with drugs during the absence of lymphocyte SDH reaction thereto. The timing of the presence of SDH reaction to drugs in the immunocompetent cells makes it possible to set the optimal daily regime of their application and to select a drug that would be most effective in each particular case.

Coenzyme Q10 supplementation downregulates the increase of monocytes expressing toll-like receptor 4 in response to 6-day intensive training in kendo athletes.

This study examined changes in toll-like receptor 4 (TLR-4)-expressing monocytes and lymphocyte subpopulations in response to continuous intensive exercise training in athletes, as well as the effect of coenzyme Q10 (CoQ10) supplementation on these changes. Eighteen male elite kendo athletes in Japan were randomly assigned to a CoQ10-supplementation group (n = 9) or a placebo-supplementation group (n = 9) using a double-blind method. Subjects in the CoQ10 group took 300 mg CoQ10 per day for 20 days. Subjects in the placebo group took the same dosage of placebo. All subjects practiced kendo 5.5 h per day for 6 consecutive days during the study period. Blood samples were collected 2 weeks before training, on the first day (day 1), third day (day 3), and fifth day of training (day 5), and 1 week after the training period (post-training) to ascertain TLR-4(+)/CD14(+) monocyte and lymphocyte subpopulations (CD3(+), CD4(+), CD8(+), CD28(+)/CD4(+), CD28(+)/CD8(+), and CD56(+)/CD3(-) cells) using flow cytometry analysis. The group × time interaction for TLR-4(+)/CD14(+) cells did not reach significance (p = 0.08). Within the CoQ10 group, the absolute number of TLR-4(+)/CD14(+) cells was significantly higher only at day 5. The placebo group showed a significant increase in the absolute number of TLR-4(+)/CD14(+) cells at day 3, day 5, and post-training (p < 0.05). There was no significant group × time interaction for any lymphocyte subpopulation. CD3(+), CD8(+), and CD56(+)/CD3(-) cells were significantly reduced at day 3 in both groups (p < 0.05). In conclusion, CoQ10 supplementation might downregulate the increase of TLR-4-expressing monocytes in response to continuous strenuous exercise training in kendo athletes.

Improvement of bacterial clearance and relief of clinical signs of Salmonella enterica serovar Typhimurium infection in pigs through upregulation of Th 1-specific responses by administration of a combination of two silicate minerals, biotite and bentonite.

Biotite and bentonite are phyllosilicate minerals that were originally used in industrial applications. Several beneficial activities of them have recently been reported, especially regulation of the immune system and antimicrobial effects. Therefore, we investigated the immune-enhancing and bacterial clearance effects of a biotite and bentonite mixture (BBM) on experimental infection of Salmonella enterica serovar Typhimurium (S. Typhimurium) to determine whether the BBM could be used as an alternative antibiotic. We administered 1% or 2% BBM as a feed supplement. We then evaluated the bacterial clearance effects of the BBM against S. Typhimurium. We also evaluated the immune-enhancing effect of the BBM through several immunological experiments that included examination of the lysozyme activity, CD4(+)/CD8(+) T lymphocyte ratio and the T-helper type 1 (Th 1) cytokine profile. The clinical signs of S. Typhimurium and the number of viable bacteria in feces and tissues were significantly decreased in both BBM groups, especially in the 2% BBM group. The BBM also markedly enhanced the lysozyme activity, CD4(+)/CD8(+) T lymphocyte ratio and expression levels of IFN-γ and IL-12 in S. Typhimurium-challenged pigs. Therefore, the BBM could be a good candidate as an alternative antibiotic that improves Th 1-specific immune responses and the bacterial clearance effect.

Effect of supplemental vitamin E on the peripheral blood leukocyte population in Japanese Black calves.

We investigated the effect of supplemental vitamin E on the peripheral blood leukocyte population in Japanese Black calves. Twenty-six calves kept at the same farm were studied. They were divided into two groups; thirteen calves received 300 IU/day of vitamin E orally from 1 to 3 months of age (VE group), and the other thirteen calves did not receive the vitamin E supplement (control group). The VE group showed a higher serum vitamin E concentration at 2 and 3 months of age compared with the control group (P<0.01). The numbers of CD3(+) cells and CD4(+) cells were higher in the VE group than in the control group, and the difference was statistically significant at 3 months of age (P<0.05). The numbers of CD21(+) cells were higher in the VE group than in the control group, and the difference was statistically significant at 2 months of age (P<0.05). The numbers of CD335(+) cells tended to be higher in the VE group than in the control group. The numbers of CD8(+) cells and CD14(+) cells tended to be higher in the VE group than in the control group at 3 and 4 months of age. This study demonstrated that the supplementation of suckling Japanese Black calves with vitamin E might affect the numbers of some immune cell types in the peripheral blood.

Crude extract of Polygonum cuspidatum stimulates immune responses in normal mice by increasing the percentage of Mac-3-positive cells and enhancing macrophage phagocytic activity and natural killer cell cytotoxicity.

Polygonum cuspidatum is a natural plant that is used in traditional Chinese herbal medicine. The crude extract of Polygonum cuspidatum (CEPC) has numerous biological effects; however, there is a lack of studies on the effects of CEPC on immune responses in normal mice. The aim of the present study was to determine the in vivo effects of CEPC on immune responses in normal mice. CEPC (0, 50, 100, 150 and 200 mg/kg) was orally administered to BALB/c mice for three weeks, following which blood, liver, and spleen samples were collected. CEPC did not significantly affect the total body weight, or tissue weights of the liver or spleen, as compared with the control mice. CEPC increased the percentages of CD3 (T-cell marker), 11b (monocytes) and Mac-3 (macrophages) positive-cells, and reduced the percentage of CD19-positive cells (B-cell marker), as compared with the control mice. CEPC (100 mg/kg) stimulated macrophage phagocytosis of blood samples but did not affect macrophage phagocytosis in the peritoneum. Activity of the splenic natural killer cells was increased in response to CEPC (50 mg/kg) treatment. Furthermore, CEPC inhibited T- and B-cell proliferation when the cells were stimulated with concanavalin A and lipopolysaccharide, respectively.