Response of brain-derived neurotrophic factor to combining cognitive and physical exercise.

Purpose: Brain-derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE.

Effect of Neuromuscular Electrical Stimulation on Brain-derived Neurotrophic Factor.

Brain-derived neurotrophic factor (BDNF) has been considered an essential mediator responsible for the beneficial effects of physical activity in preventing cognitive impairment. This study aimed at examining the effects of a single bout of neuromuscular electrical stimulation (NMES) on levels of BDNF in the plasma and on cognitive performance in healthy adult men. Thirteen healthy adult men participated in three experimental sessions.

A Protease Inhibitor with Induction Therapy with Natural Interferon-β in Patients with HCV Genotype 1b Infection.

The restoration of innate immune responses has potential as a novel therapeutic strategy for chronic hepatitis C (CHC). We compared the efficacy and safety of induction therapy (IT) with natural interferon-β (n-IFN-β) followed by pegylated-IFN-α/ribavirin (PR) alone (group A, n = 30) and IT with a protease inhibitor (PI) (simeprevir or vaniprevir)/PR (group B, n = 13) in CHC patients with genotype 1b and high viral loads. During IT with nIFN-β, virologic response rates in group A and group B were 10% and 8% (p = 0.

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days.

Restoration of innate and adaptive immune responses by HCV viral inhibition with an induction approach using natural interferon-beta in chronic hepatitis C.

Chronic hepatitis C (CHC) is a serious medical problem necessitating more effective treatment. This study investigated the hypothesis that an induction approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin (standard of care: SOC) for 48 weeks (novel combination treatment: NCT) would increase the initial virologic response rate and restore innate and adaptive immune responses in CHC. Seven CHC patients with a high viral load and genotype 1b were treated with NCT.

Cisplatin-induced acute renal failure in mice is mediated by chymase-activated angiotensin-aldosterone system and interleukin-18.

Mechanism(s) of cisplatin-induced acute renal failure, as manifested by increases in blood urea nitrogen and creatinine, was evaluated in relation to production and activation of endogenous mediator(s) in mice. In interleukin (IL)-18-deficient (IL-18KO) mice, cisplatin failed to induce acute renal failure. Administration of recombinant IL-18 prior to cisplatin restored acute renal failure in IL-18KO mice.

Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke.

Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4(+)T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4(+)T cells.

Immunoregulatory effects of adsorptive granulocyte and monocyte apheresis in patients with drug refractory Crohn's disease.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function.

Abrogation of Treg function deteriorates rheumatoid arthritis.

An early prognostic indicator which warns of progressive joint destruction of rheumatoid arthritis (RA) was explored using a novel suspension-array technique in moderate (Steinbrocker stage I and II) and severe (Steinbrocker stage IV) RA patients. DNA microarray analysis of peripheral blood lymphocytes showed significant increase of interleukin (IL)-2 receptor α-chain (CD25) gene expression, a regulatory T cell (Treg) surface marker in severe RA patients. In contrast, suspension array, a comprehensive bead-based enzyme-linked immunosorbent assay (ELISA), revealed decreased production of IL-10 and increased production of interferon (IFN)-γ in sera in the incipient stage of the aggressive disease process.

Infliximab therapy impacts the peripheral immune system of immunomodulator and corticosteroid naïve patients with Crohn's disease.

Background/aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX.

Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke.

Acute inflammation in the poststroke period exacerbates neuronal damage and stimulates reparative mechanisms, including neurogenesis. However, only a small fraction of neural stem/progenitor cells survives. In this report, by using a highly reproducible model of cortical infarction in SCID mice, we examined the effects of immunodeficiency on reduction of brain injury, survival of neural stem/progenitor cells, and functional recovery.

Interleukin-18 prevents apoptosis via PI3K/Akt pathway in normal human keratinocytes.

Interleukin-18 (IL-18) is a pleiotropic cytokine expressed in both immune and non-immune cells. In the present study, we demonstrate an anti-apoptotic role of IL-18 in normal human neonatal foreskin epidermal keratinocytes (NHEK-F). Cultured NHEK-F spontaneously produced the active form of IL-18.

A role for IL-18 in human neutrophil apoptosis.

Decreased neutrophil apoptosis is associated with persistent inflammation, the severity of which correlates with serum IL-18 levels. IL-18 receptors as well as Toll-like receptors, including Toll-like receptor 4, a receptor for LPS, possess a highly conserved intracellular domain called "Toll-IL-1R domain" and activate overlapping signaling pathways. Here, we show that IL-18 modulates neutrophil apoptosis and compare its mechanism of action with LPS.

Protection of CD8+ T cells from activation-induced cell death by IL-18.

Role of IL-18 on proliferation and survival of CD8+ T cells, activated by immobilized anti-CD3 antibody (anti-CD3), was examined. Proliferation and survival of activated T cells, especially that of CD8+ T cells, were impaired by IL-18 deficiency [IL-18 knockout (KO)]. After 3 days of culture with anti-CD3, the number of living CD8+ T cells from IL-18KO mice was approximately 25% of that from wild-type (WT) mice but was increased to the same level as WT cells by the addition of IL-18.

Neutrophil activation and arteritis induced by C. albicans water-soluble mannoprotein-beta-glucan complex (CAWS).

We have established a mouse model which shows the symptoms of coronary arteritis after consecutive injections of CAWS, which is released from Candida albicans. In this study, we examined neutrophil activation in the initial period after CAWS injection intraperitoneally. During 10 min to 16 h after the injection, blood profiles and neutrophil functions were determined.

IL-18 mediates the formation of stress-induced, histamine-dependent gastric lesions.

A role of IL-18 in the induction of gastric lesions by water immersion and restraint stress (WRS) was investigated. When wild-type BALB/c mice were exposed to WRS, levels of IL-18 in the serum and stomach increased rapidly with the development of acute gastric lesions. In IL-18-deficient mice [IL-18 knockout (KO) mice] similarly exposed to WRS, no gastric lesions were observed, but the administration of IL-18 before exposure to WRS resulted in the induction of WRS-induced gastric lesions.

Production of IL-13 in spleen cells by IL-18 and IL-12 through generation of NK-like cells.

Treatment of Nylon wool-passed cells (NWC) prepared from the spleen of C57BL/6 mice with IL-18 and IL-12, but not with IL-18 alone, resulted in induction of IFN-gamma, a Th1 cytokine, and GM-CSF at 24 h, and IL-13, a Th2 cytokine at 72 h. The induction of IL-13 was suppressed by anti-GM-CSF antibody, indicating involvement of GM-CSF in IL-13 production. When NWC incubated with IL-18 and IL-12 for 72 h ("primary treatment") were treated again with the same cytokines ("secondary treatment"), IL-13 was induced much more quickly than observed in the primary treatment.

Chylomicron remnants stimulate release of interleukin-1beta by THP-1 cells.

Recent findings suggest that the oxidative modification of low-density lipoproteins (LDL) and an increase in triglyceride-rich lipoprotein particles including chylomicron remnants contribute to the progression of atherosclerosis, as does the inflammatory response. We therefore examined whether and how these lipoproteins affected interleukin (IL)-1beta release and mRNA expression for IL-1beta and IL-18 in THP-1 cells, a human monocyte cell line. Chylomicron remnants increased IL-1beta release into the conditioned medium by THP-1 in a dose- and time-dependent manner.

IL-18; a cytokine translates a stress into medical science.

Psychological/physical stresses have been reported to exacerbate auto-immune and inflammatory diseases. To clarify a mechanism by which non-inflammatory stresses disrupt host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via ACTH and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form which was released into plasma.

Role of interleukin 18 in nitric oxide production and pancreatic damage during acute pancreatitis.

The release of the immunomodulator, interleukin 18 (IL-18) into sera early in acute pancreatitis (AP) corresponds to disease severity. IL-18 induces nitric oxide (NO), which is involved in the pathophysiology of pancreatitis. The objective of this study was to clarify the role of IL-18 in pathogenesis and NO production during early AP using recombinant mouse (rm) IL-18 protein and IL-18 gene knockout (KO) mice.

A role of the adrenal gland in stress-induced up-regulation of cytokines in plasma.

To reveal a pathway by which psychological/physical stresses influence host defense capability, responses to immobilization stress in mice were investigated, focusing on a multifunctional cytokine, interleukin-18 (IL-18). Immobilization stress induced interleukin-18 accumulation in plasma and in the adrenal gland. Inhibition on ACTH resulted in suppressed levels of IL-18 both in plasma and the adrenal gland.

Plasma interleukin-18 concentration: a novel marker of myocardial ischemia rather than necrosis in humans.

Objective: Myocardial ischemia contributes to cytokine expression in the myocardium in animals; therefore, plasma interleukin-18 concentration may be a good marker of myocardial ischemia/injury in patients with possible acute coronary syndrome. We sought to determine whether increases in plasma interleukin-18 concentrations might be indicative of myocardial ischemia in patients with acute coronary syndrome.

Methods: Plasma interleukin-18 concentrations were assessed in 27 acute coronary syndrome patients in whom creatine kinase activity was within normal range on admission, in addition to 10 controls.

Selective granulocyte and monocyte apheresis as a new adjunct to enhance the efficacy of interferon-alpha + ribavirin in patients with high plasma hepatitis C virus.

Background And Aim: Selective granulocyte and monocyte/macrophage adsorptive apheresis is to increase the turnover of infected leucocytes and has increased CD4+ T cells, which are necessary for actions of interferon-alpha on hepatitis C virus. Therefore, granulocyte and monocyte apheresis was to enhance the efficacy of interferon + ribavirin.

Methods: Fifteen patients, 12 had interferon resistant hepatitis C virus and 3 were interferon naive.

A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma IL-18 upregulation.

Psychological/physical stresses are known to cause relapses of autoimmune and inflammatory diseases. To reveal a mechanism by which noninflammatory stresses affect host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via adrenocorticotropic hormone (ACTH) and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form, which was released into plasma.