Effects of adalimumab therapy on disease activity and interferon-γ-mediated biochemical pathways in patients with rheumatoid arthritis.

In patients with rheumatoid arthritis (RA), overwhelming inflammatory activity and immune activation are indicated by elevated concentrations of immune activation markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neopterin. Furthermore, accelerated tryptophan (Trp) degradation by the enzyme indoleamine 2,3-dioxygenase (IDO) is detectable in blood samples of patients by an increased kynurenine (Kyn) to Trp ratio (Kyn/Trp). This study comprises 22 patients (20 women, 2 men) with long-standing, moderate to severe RA, who were treated with a monoclonal tumor necrosis factor (TNF)-antibody (Adalimumab 40 mg subcutaneously every other week) in addition to their concomitant, but inadequate anti-rheumatic therapies.

Interferon-gamma-mediated pathways and in vitro PBMC proliferation in HIV-infected patients.

HIV infection is characterized by progressive immunodeficiency: HIV-infected peripheral blood mononuclear cells (PBMCs) cannot properly react to stimulation with allo-antigens and mitogens. In this study, we examined interferon-gamma (IFN-gamma)-mediated pathways and the proliferative response of mitogen-stimulated HIV-infected PBMCs in vitro. PBMCs of 30 HIV-infected patients were stimulated with the mitogens concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM).

Non-peptidic delta-opioid receptor antagonists suppress mitogen-induced tryptophan degradation in peripheral blood mononuclear cells in vitro.

Opioid receptors are expressed not only on neuroendocrine cells but also on immunocompetent cells such as lymphocytes, monocytes and macrophages. micro-Opioid receptor agonists were found to exert immunosuppressive effects, whereas delta-opioid receptor agonists have been shown to act as immunostimulants. delta-Opioid receptor agonists stimulate T and B cells and activate granulocytes and monocytes, conversely, immunostimulation can be blocked by the non-peptidic delta-opioid receptor antagonist (NTI).

Diminished quality of life in patients with cancer correlates with tryptophan degradation.

Purpose: Quality of life (QoL) is frequently impaired in patients suffering from malignant disease. Disturbed metabolism of neurotransmitter serotonin might be crucially involved, and serotonin-precursor tryptophan is degraded during pro-inflammatory immune response. In this study, we compared QoL and fatigue self-rating scores of patients with various types of malignancy with tryptophan metabolic changes and immune activation status.

CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of Indoleamine-2,3-dioxygenase.

Bone marrow transplantation (BMT) under costimulation blockade induces mixed chimerism and tolerance in rodent models. Recent data, predominantly from in vitro studies, suggest that in addition to blocking the CD28 costimulation pathway CTLA4Ig also acts through upregulating the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Here we demonstrate that even though CTLA4Ig is critically required for the induction of chimerism and tolerance in a murine model of nonmyeloablative BMT, IDO activity is not.

Hyperhomocysteinaemia and immune activation in patients with cancer.

Background: Recently, homocysteine production was observed in tumour cell lines and homocysteine was proposed as a tumour marker. Furthermore, homocysteine production by activated immunocompetent cells was demonstrated.

Methods: In this study, homocysteine metabolism and immune activation status were investigated in 128 patients suffering from various types of cancer (haematological disorders, lung cancer, gastrointestinal tumours, gynaecological cancer and tumours of other localisation) and healthy age-matched controls.

Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients.

Background: Indoleamine (2,3)-dioxygenase (IDO) catalyses the initial, rate-limiting step in the degradation of the essential amino acid tryptophan. Via tryptophan deprivation, IDO activity suppresses T cell proliferation and differentiation and is thought to be a fundamental immune escape mechanism for tumor cells.

Objective And Methods: To investigate the potential role of tryptophan degradation as a prognostic marker, serum tryptophan and kynurenine concentrations and the kynurenine-to-tryptophan ratio (kyn/trp) in 87 patients with malignant melanoma were compared to the course of the disease and to concentrations of the immune activation marker neopterin.

Calcium-pterin suppresses mitogen-induced tryptophan degradation and neopterin production in peripheral blood mononuclear cells.

Antitumor activity of a calcium-pterin suspension has been described in vitro and in animal model systems. Recent studies provide some evidence that this effect involves immune-mediated mechanisms. We investigated the influence of calcium-pterin on freshly isolated human peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin and concanavalin A in vitro.

Antitumoral activity of interferon-gamma involved in impaired immune function in cancer patients.

Insufficient immunosurveillance is an important aspect in early tumorigenesis and in the pathogenesis of malignant disease. In the later course of cancer, the development of immunodeficiency is considered the major reason for disease progression and death. Within the anti-tumoral host defense reaction, Th1-type cytokine interferon-gamma (IFN-gamma) is of particular relevance.

Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells.

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-gamma.

Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease.

Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cytokine interferon-gamma, which is released by activated T-lymphocytes.

Bariatric surgery cannot prevent tryptophan depletion due to chronic immune activation in morbidly obese patients.

Background: Increased activity of the immuno-modulatory enzyme indoleamine-2,3-dioxygenase (IDO) during immune activation, results in tryptophan depletion. Tryptophan metabolic changes reduce serotonin production and cause mood disturbances, depression, and impaired satiety, ultimately leading to increased food intake and obesity. Bariatric surgery significantly diminishes immune mediators by substantial weight reduction.

Cognitive deterioration in Alzheimer's disease is accompanied by increase of plasma neopterin.

The pro-inflammatory reaction of the immune system is a feature of healthy aging and might influence the progression of Alzheimer's disease (AD). Neopterin is a pteridine derivative, released from macrophages upon stimulation with pro-inflammatory cytokine interferon-gamma. Forty-three probable AD patients were investigated at baseline and follow up (14.

Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells.

Purpose: The pathologic interactions between tumor and host immune cells within the tumor microenvironment create an immunosuppressive network that promotes tumor growth and protects the tumor from immune attack. In this study, we examined the contribution of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) on this phenomenon.

Experimental Design: Expression of IDO was analyzed in colorectal cancer cell lines by reverse transcription-PCR and functional enzyme activity was assessed by high-pressure liquid chromatography.

Method for urinary neopterin measurements by HPLC.

In the June 2004 issue of the Journal, Drs. Ribeiro de Castro and coworkers described a new method to determine neopterin concentrations in urine by HPLC and UV-absorption detection [de Castro MR, Di Marco GS, Arita DY, Teixeira LC, Pereira AB, Casarini DE. Urinary neopterin quantification by reverse-phase high-performance liquid chromatography with ultraviolet detection.

Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells.

Hyperhomocysteinemia is regarded as an independent risk factor for vascular diseases, and homocysteine is supposed to contribute to oxidative stress and endothelial damage. Statin therapy is an established intervention to reduce the risk of acute events in patients suffering from cardiovascular diseases. Apart from their lipid-lowering capacity, statins also exert anti-inflammatory and antioxidant effects.

Relationship between homocysteine and neopterin concentrations in patients with gynecological cancer.

Elevated concentrations of vascular risk factor homocysteine have been described in patients with malignant diseases, and homocysteine was supposed to be useful as tumor marker. Likewise, elevated concentrations of Th1-type immune activation marker neopterin are frequently observed in patients suffering from cancer and serve as prognostic marker for the survival of patients. In this study, the relationship between homocysteine and neopterin concentrations was examined in 18 patients with gynecological cancer.

Tryptophan degradation increases with stage in patients with rheumatoid arthritis.

Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The proinflammatory cytokine interferon-gamma in various cells, including monocytes, induces the enzyme indoleamine (2,3)-dioxygenase (IDO), which converts tryptophan to kynurenine. In sera of 22 patients (17 women and 5 men) with RA stages 1 to 4 according to Steinbrocker, the concentrations of tryptophan and kynurenine were measured by high-pressure liquid chromatography.

Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro.

Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process.

Resveratrol suppresses interferon-gamma-induced biochemical pathways in human peripheral blood mononuclear cells in vitro.

A wide range of biological activities of resveratrol (3,5,4'-trihydroxystilbene) in vitro and in vivo has been proved, including antioxidant, antitumor, and also anti-inflammatory effects. Resveratrol found in, e.g.

Monitoring tryptophan metabolism in chronic immune activation.

The essential amino acid tryptophan is a constituent of proteins and is also a substrate for two important biosynthetic pathways: the generation of neurotransmitter 5-hydroxytryptamine (serotonin) by tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides. The latter pathway is initiated by the enzymes tryptophan pyrrolase (tryptophan 2,3-dioxygenase, TDO) and indoleamine 2,3-dioxygenase (IDO). TDO is located in liver cells, whereas IDO is expressed in a variety of cells including monocyte-derived macrophages and dendritic cells and is preferentially induced by Th1-type cytokine interferon-gamma.

Homocysteine and serum markers of immune activation in primary dystonia.

The cause of primary dystonia remains unknown. Several reports point to immune system disturbances in primary dystonia and a recent study demonstrated hyperhomocysteinemia in cervical dystonia. Homocysteine (HCY) is an amino acid and elevated HCY concentrations were shown to be associated with immune system activation and increased neopterin serum concentrations.

Tryptophan degradation in patients with gynecological cancer correlates with immune activation.

Tryptophan degradation by the enzyme indoleamine-(2,3)-dioxy genase (IDO) and neopterin production are induced within cellular immune activation by stimulation of monocyte-derived macrophages and dendritic cells with cytokine interferon-gamma. Deprivation of tryptophan represents an important antimicrobial and antitumoral immune defence mechanism but it also suppresses T-cell proliferation. Recently tryptophan degradation by tumor cells was proposed as strategy to escape immune response.