2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver.

Rheumatoid arthritis (RA) is significantly associated with glycolysis. This study used 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, to treat rats with collagen-induced arthritis (CIA) and investigate the metabolic regulatory mechanism of glycolysis in the disease. 2-DG significantly alleviated CIA. Metabolomics and transcriptomics, as well as their integrative analysis, detected significant changes in the pathways of bile secretion, cholesterol and linoleic acid metabolism in the plasma, liver and spleen during the CIA process and the opposite changes following 2-DG treatment, whereas the expression of the genes regulating these metabolic pathways were changed only in the spleen. In the rat liver, levels of (S)-5-diphosphomevalonic acid in the terpenoid backbone biosynthesis pathway were significantly decreased during CIA progression and increased following 2-DG treatment, and levels of taurochenodeoxycholic acid in the pentose and glucuronate interconversions pathway showed the opposite results. In the spleen, levels of 3-methoxy-4-hydroxyphenylglycol glucuronide in bile secretion and 12(S)-leukotriene B4 in arachidonic acid metabolism were significantly decreased during CIA progression and increased following 2-DG treatment. The changes in the gene-metabolite network of bile secretion in the spleen correlated with a decreased plasma L-acetylcarnitine level in CIA rats and an increase following 2-DG treatment. Our analysis suggests the involvement of spleen and liver metabolism in CIA under the control of glycolysis.

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. RESULTS: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT. In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

Innate Lymphocytes in Inflammatory Arthritis.

Inflammatory arthritis (IA) refers to a group of chronic diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and other spondyloarthritis (SpA). IA is characterized by autoimmune-mediated joint inflammation and is associated with inflammatory cytokine networks. Innate lymphocytes, including innate-like lymphocytes (ILLs) expressing T or B cell receptors and innate lymphoid cells (ILCs), play important roles in the initiation of host immune responses against self-antigens and rapidly produce large amounts of cytokines upon stimulation. TNF (Tumor Necrosis Factor)-α, IFN (Interferon)-γ, Th2-related cytokines (IL-4, IL-9, IL-10, and IL-13), IL-17A, IL-22, and GM-CSF are involved in IA and are secreted by ILLs and ILCs. In this review, we focus on the current knowledge of ILL and ILC phenotypes, cytokine production and functions in IA. A better understanding of the roles of ILLs and ILCs in IA initiation and development will ultimately provide insights into developing effective strategies for the clinical treatment of IA patients.

Parameters of the Immune System and Vitamin D Levels in Old Individuals.

Aim: The increased number of individuals older than 80 years, centenarians, and supercentenarians is not a synonym for healthy aging, since severe infections, hospitalization, and disability are frequently observed. In this context, a possible strategy is to preserve the main characteristics/functions of the immune system with the aim to cause less damage to the organism during the aging process. Vitamin D acts on bone marrow, brain, breast, malignant cells, and immune system and has been recommended as a supplement. We aimed to evaluate whether immune parameters and vitamin D serum levels are correlated. Methods: We evaluated some features of the immune system using the peripheral blood of individuals older than 80 years (n = 12) compared to young subjects (n = 10). In addition, we correlated these findings with vitamin D serum levels. Results: Old individuals presented metabolic parameters of healthy aging and maintained preserved some features of immunity such as CD4/CD8 ratio, and low production of pro-inflammatory cytokines after stimulus. On the other hand, we observed increase in the frequency of myeloid-derived suppressor cells, reduction in circulating leukocytes, in the percentage of total CD8+, and in CD8+ Naïve T cells, in addition to increase in the percentage of CD8+ effector memory re-expressing CD45RA (EMRA) T cells. We found seropositivity for CMV in 97.7%, which was correlated with the decrease of CD8+ Naïve T cells and increase in CD8+ EMRA T cells. Vitamin D levels were insufficient in 50% of old individuals and correlated positively with total CD8+ T cells and negatively with CD8+ EMRA T cells. Conclusion: In the studied population, longevity was correlated to maintenance of some immune parameters. Considering the limitations of the study as size of the sample and lack of functional assays, it was found that vitamin D in old individuals was correlated to some features of the immune system, mainly in the CD8 compartment.

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.

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.

The Yin and Yang of Innate Lymphoid Cells in Cancer.

The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes.

Regulatory T cell therapy for type 1 diabetes: May the force be with you.

Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin producing beta cells. Regulatory T cells (Tregs) have been shown to be defective in this setting. Immuno-therapies targeting T cells, and resetting the balance between T effectors and Tregs, have had some initial success in preserving beta cell function. With a goal to use Tregs themselves as a novel therapeutic, we developed a technique to isolate and expand Tregs from patients with T1DM. These ex vivo expanded CD4(+)CD127(lo/-)CD25(+) cells exhibit improved function and retain their T cell receptor diversity. These cells have subsequently been used in phase I clinical trials in patients with recent onset T1DM. The infusions were well tolerated, with no safety concerns. The studies are too small to assess efficacy definitively, although some individuals exhibit stable beta cell function over intervals as long as 2 years. These efforts set the stage for a larger phase II effort in new onset T1DM, and combination studies with other drugs, as well as efforts in other autoimmune diseases.

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.

Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

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.

GABAergic neurons in cerebellar interposed nucleus modulate cellular and humoral immunity via hypothalamic and sympathetic pathways.

Our previous work has shown that cerebellar interposed nucleus (IN) modulates immune function. Herein, we reveal mechanism underlying the immunomodulation. Treatment of bilateral cerebellar IN of rats with 3-mercaptopropionic acid (3-MP), a glutamic acid decarboxylase antagonist that reduces γ-aminobutyric acid (GABA) synthesis, enhanced cellular and humoral immune responses to bovine serum albumin, whereas injection of vigabatrin, a GABA-transaminase inhibitor that inhibits GABA degradation, in bilateral cerebellar IN attenuated the immune responses. The 3-MP or vigabatrin administrations in the cerebellar IN decreased or increased hypothalamic GABA content and lymphoid tissues' norepinephrine content, respectively, but did not alter adrenocortical or thyroid hormone levels in serum. In addition, a direct GABAergic projection from cerebellar IN to hypothalamus was found. These findings suggest that GABAergic neurons in cerebellar IN regulate immune system via hypothalamic and sympathetic pathways.

Acupuncture for sleep quality, BDNF levels and immunosenescence: a randomized controlled study.

Poor sleep in elderly populations is associated with detrimental neuropsychological, and physiological changes including premature immunosenescence and reduced brain derived neurotrophic factor (BDNF). Here, we evaluated the effects of acupuncture on sleep quality, psychological distress and immunosenescence in elderly, as well as effects on BDNF levels. Forty-eight community-dwelling elderly were randomized into true or placebo acupuncture, and intervention consisted of ten sessions. Sleep quality, depression and stress scores were evaluated by the Pittsburgh sleep quality index (PSQI), beck depression inventory (BDI II) and perceived stress scale (PSS), respectively, before and after the intervention. Lymphocyte subsets commonly associated with stress, sleep impairment and immunosenescence were phenotyped by flow cytometry. BDNF plasma levels were assessed by ELISAs. Acupuncture was highly effective for improving sleep quality (-53.23%; p<0.01), depression (-48.41%; p<0.01), and stress (-25.46%; p<0.01). However, neither lymphocyte subpopulations nor BDNF levels changed following the intervention.

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.

Immune-enhancing activity of polysaccharides from Cyrtomium macrophyllum.

The goal of the present study was to investigate the immune-enhancing activity of polysaccharides from Cyrtomium macrophyllum (CMP). Two experiments were carried out. In immunosuppression experiment, the immune-enhancing effect of CMP in immunosuppressive mice was performed. The results showed that CMP at high and medium doses was able to overcome the CY-induced immunosuppression, significantly increases the thymus and spleen indices, enhances lymphocyte proliferation activity and macrophage function, improves immunoglobulin and cytokines levels compared with negative control group. In macrophage immunomodulatory experiment, the immune-enhancing effect of CMP in RAW264.7 cells was measured. The results showed that CMP induced the elevation of NO production, TNF-α secretion and iNOS protein of RAW264.7 cells. CMP can also strongly increase NF-κB levels in nuclear, which is an important transcription factor that can modulate expressions of iNOS, NO and TNF-α. Therefore, the CMP could be an effective immunomodulatory agent.

A low-molecular-weight dialysable leukocyte extract selectively enhances development of CD4⁺RORγt⁺ T cells and IL-17 production.

A low-molecular-weight (under 10 kDa) dialysable leukocyte extract (called transfer factor, TF) has been shown to be a prospective substance to improve or modulate immune response in autoimmunity, inflammation, infectious diseases or cancers. However, the use of TF has been limited by the absence of any data on the mechanism of its action. Here we show that TF prepared from peripheral blood leukocytes of healthy human donors displays multiple regulatory effects on individual parameters of the immune system. TF decreases proliferation of T and B lymphocytes and partially alters the production of cytokines and nitric oxide by activated macrophages. TF also inhibits production of T helper 1 (Th1) cytokines interleukin 2 (IL-2) and interferon γ, slightly stimulates production of Th2 cytokine IL-10 and considerably enhances the secretion of IL-17 by activated mouse spleen T cells. At the molecular level, TF enhances expression of genes for transcription factor RORγt and for IL-17. The enhanced expression of the RORgt gene corresponds with an increase in the number of RORγt⁺CD4⁺ Th17 cells and with enhanced IL-17 production. In contrast, the expression of the Foxp3 gene and the proportion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells are not significantly changed in the presence of TF. These results suggest that the activation of pro-inflammatory Th17 cells, which have multiple immunoregulatory properties, could be the main mechanism of the immunomodulatory action of a low-molecular-weight leukocyte extract.