Cacao extracts suppress tryptophan degradation of mitogen-stimulated peripheral blood mononuclear cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Theobroma cacao L. (Sterculiaceae) have been used as food and a remedy for more than 4000 years. Today, about 100 therapeutic applications of cacao are described involving the gastrointestinal, nervous, cardiovascular and immune systems. Pro-inflammatory cytokine interferon-gamma and related biochemical pathways like tryptophan degradation by indoleamine 2,3-dioxygenase and neopterin formation are closely associated with the pathogenesis of such disorders. AIM OF THE STUDY: To determine the anti-inflammatory effect of cacao extracts on interferon-gamma and biochemical consequences in immunocompetent cells. MATERIALS AND METHODS: Effects of aqueous or ethanolic extracts of cacao were examined on mitogen-induced human peripheral blood mononuclear cells (PBMC) of healthy donors and on lipopolysaccharide-stimulated myelomonocytic THP-1 cells. Antioxidant activity of extracts was determined by oxygen radical absorption capacity (ORAC) assay. RESULTS: In mitogen-stimulated PBMC, enhanced degradation of tryptophan, formation of neopterin and interferon-gamma were almost completely suppressed by the cacao extracts at doses of > or = 5 microg/mL. Cacao extracts had no effect on tryptophan degradation in lipopolysaccharide-stimulated THP-1 cells. CONCLUSIONS: There is a significant suppressive effect of cacao extracts on pro-inflammatory pathways in activated T-cells. Particularly the influence on indoleamine 2,3-dioxygenase could relate to some of the beneficial health effects ascribed to cacao.

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. Influence of calcium-pterin on tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase (IDO) and on neopterin production was monitored in supernatants of cells. Increased neopterin concentrations as well as accelerated tryptophan degradation have been found to predict poor prognosis in patients with cancer, and both these immunobiochemical pathways are induced by the pro-inflammatory cytokine interferon-gamma. Compared to unstimulated cells, mitogens induced degradation of tryptophan and formation of neopterin in PBMC, and upon addition of calcium-pterin, both biochemical results were suppressed in a dose-dependent way. Thus, calcium-pterin suppresses immunological pathways in vitro that in patients with malignant diseases characterize an unfavorable prognosis. The effect of the compound to suppress IDO activity could be of considerable relevance for the antitumoral effect of the compound because activation of the enzyme is considered as an immune-escape mechanism of tumor cells.

Beer down-regulates activated peripheral blood mononuclear cells in vitro.

Moderate consumption of alcoholic beverages is suggested to reduce cardiovascular risk. Within this context, most attention is drawn to antioxidant ingredients of wine, but also beer was found to be beneficial. Potential effects of three different types of beer including alcohol-free beer were investigated using freshly isolated human peripheral blood mononuclear cells stimulated with the mitogen phytohaemagglutinin in vitro. Neopterin production and tryptophan degradation were monitored in culture supernatants to determine effects of test substances on immunobiochemical pathways induced by interferon-gamma. In a subgroup of experiments also production of interferon-gamma was measured. Compared to unstimulated cells, phytohaemagglutinin increased production of neopterin and also triggered the degradation of tryptophan (all p < 0.01). All types of beer (2-4% dilution) were found to counteract these stimulation-induced effects and significant reduction of neopterin formation and tryptophan degradation was observed (p < 0.01). Data demonstrate that beer reduces production of neopterin and degradation of tryptophan, both these biochemical pathways are induced during cell-mediated immune response. Data suggest that the immunosuppressive capacity of beer may relate to its anti-inflammatory nature.

Histamine suppresses neopterin production in the human myelomonocytoma cell line THP-1.

Histamine, an important inflammatory mediator in allergic diseases and asthma, was reported to have modulatory effects on T cells by down-regulating Th1-type cell cytokines like interleukin 2 (IL-2) and interferon-gamma (IFN-gamma). In this study we examined the effect of histamine and the histamine-receptor antagonists cimetidine and diphenhydramine on the production of neopterin after stimulation with IFN-gamma in the myelomonocytoma cell line THP-1. Increasing concentrations of histamine markedly suppressed IFN-gamma induced neopterin formation. Simultaneous preincubation of THP-1 cells with histamine, IFN-gamma and different concentrations of the H(2)-receptor antagonist cimetidine showed a clear antagonizing effect on neopterin formation. In contrast, the H(1)-receptor antagonist diphenhydramine was not able to abrogate the suppressive effect of histamine on neopterin production. Our results suggest, that histamine may be a potent inhibitor of effects or mechanisms induced by IFN-gamma in monocytes/macrophages. Cimetidine, and possibly other H(2)-receptor antagonists, may reverse down-regulatory actions of endogenously formed histamine on activated monocytic cells.