Possible role of cytokine‐induced tryptophan degradation in anaemia of inflammation

Weiss, Günter; Schroecksnadel, Katharina; Mattle, Verena; Winkler, Christiane; Konwalinka, Guenther; Fuchs, Dietmar

doi:10.1046/j.0902-4441.2003.00197.x

Cited by 50 publications

(48 citation statements)

References 25 publications

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“…In line with this, in patients with inflammation-induced anemia, Kyn/Trp was found to inversely correlate with haemoglobin levels [94,95] . Accelerated Trp breakdown was reported in patients with coronary heart disease [96] and IDO activity correlated significantly with several risk factors for atherosclerosis in the Cardiovascular Risk in Young Finns Study [97] .…”

supporting

confidence: 61%

Antioxidants, inflammation and cardiovascular disease

Mangge¹

2014

WJC

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Multiple factors are involved in the etiology of cardiovascular disease (CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells, leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species (ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or, and even more likely, due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress, however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover, molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signaling pathways involved in the regulation of immunological, metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response, interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase (IDO) in monocyte-derived macrophages, fibroblasts, endothelial and epithelial cells. Neopterin, a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase (NOS) is induced in several cell types to generate nitric oxide (NO). NO, despite its low reactivity, is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin (BH4), which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite (ONOO -) is formed solely in the presence of superoxide anion (O2 -). Neopterin and kynurenine to tryptophan ratio (Kyn/Trp), as an estimate of IDO enzyme activity, are robust markers of immune activation in vitro and in vivo . Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise, a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C, -E and -B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites, BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD. REVIEWSubmit a

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supporting

confidence: 61%

Antioxidants, inflammation and cardiovascular disease

Mangge¹

2014

WJC

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“…This is especially important for people suffering from infectious diseases including HIV, tuberculosis and malignant influenza (as demonstrated by the large geographic variation in mortality during the Spanish Flu pandemic), due to the combination of high protein/amino acid degradation and large requirements for some of the amino acids (notably glutamine and sulphur amino acids, but also others) in order to obtain an optimal immunological response [4,6,7,8,9,10,11]. Several animal foods, but not all, can also be important sources of various conditionally essential nutrients, such as nucleic acids and taurine, and of lipid components such as longchain polyunsaturated fatty acids, myo-inositol and choline.…”

Section: Combining Plant Food and Animal Foodsmentioning

confidence: 99%

“…The infections, in turn, lead to significant metabolic changes with substantial enhancement of the rate of degradation or excretion of several important nutrients, including total protein, sulphur amino acids, tryptophan and various vitamins [4,7,8,9]. Infectious diseases, therefore, cause exacerbation of protein-energy malnutrition and various vitamin deficiency disorders associated with poor diets [4].…”

Section: Introductionmentioning

confidence: 99%

Use of dried kapenta (Limnothrissa miodon and Stolothrissa tanganicae) and other products based on whole fish for complementing maize-based diets

Haug¹,

Christophersen²,

Kinabo³

et al. 2010

African Journal of Food, Agriculture, Nutrition and Development

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Poor nutritional status both for children and adults is highly prevalent in those parts of sub-Saharan Africa where maize is a dominant staple. Maize is not a complete food, and if the child's diet is only based on white maize, it may be deficient in calcium, vitamin A, vitamin C, vitamin B 12 , vitamin E, vitamin K, folate, riboflavin, pantothenic acid, niacin, potassium and iron. Inadequate intake of essential amino acids, vitamins, minerals and trace elements is associated with reduced growth, weakening of immunological functions and enhanced morbidity and mortality from infectious diseases, including measles, diarrhoeal diseases, parasite infestations, tuberculosis and HIV disease. Pregnant women and people suffering from infectious diseases, including HIV and tuberculosis, need a diet rich in protein and micronutrients. During pregnancy, growth requirements for the foetus must be covered. Infections lead to significant metabolic changes with enhanced rates of degradation or excretion of several nutrients including total protein, essential amino acids and vitamins. The diet must now contain higher amounts of nutrients than required by a healthy child or adult person in order to prevent the development of protein malnutrition and micronutrient deficiencies that will in turn easily lead to weakening of immunological functions. The purpose of the study was i) to analyse the nutrient composition of kapenta, and compare it to other animal products, and ii) to calculate the quantity of these products needed to cover the recommended dietary intake of several nutrients. Nutrient compositions of whole dried kapenta and Norwegian fish powder (fish protein concentrate type B) were found to be similar. It is shown that products made from whole fish are qualitatively superior to fish fillet and other animal products because they are much better sources of minerals and trace elements such as calcium, iron and zinc. They are also good sources of vitamin B 12 and other bioactive substances such as membrane lipids, taurine and nucleic acids. Calculations of the improvements in nutrient intake if a maize-based diet is supplemented with minor amounts of a micronutrient-and protein-rich food like dried kapenta, or fish meal, was shown to give a balanced diet covering most of the nutrient requirements. It should be noted that patients suffering from chronic infectious diseases such as AIDS and tuberculosis have higher nutrient requirements (for protein, essential amino acids and several micronutrients) compared to healthy persons.

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“…Tryptophan availability is rate limiting for protein biosynthesis and thus cell growth [11]. Shunting available tryptophan through the kynurenine pathway depletes tryptophan in the local tissue environment.…”

Section: Discussionmentioning

confidence: 99%

Is the L-tryptophan metabolite quinolinic acid responsible for eosinophilic fasciitis?

Noakes

Spelman²,

Williamson

2006

Clin. Exper.Med.

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The eosinophilia-myalgia syndrome is accompanied by alterations in L-tryptophan metabolism with elevated levels of L-kynurenine and quinolinic acid having been recorded. It has been suggested that this is due to activation of indoleamine 2,3-dioxygenase by interferon-gamma. It is unknown whether these products of tryptophan metabolism play a role in the pathogenesis of this syndrome and the closely related condition of eosinophilic fasciitis. To explore this possibility, the principal author (RN) received a series of subcutaneous injections of quinolinic acid. A total of 1200 mg was administered over a 1-month period. Peripheral blood eosinophil counts were monitored and biopsies taken for H&E and immunohistochemical stains. Over the 1-month period the eosinophil count rose from 0.3x10(9)/l to 0.8x10(9)/l before falling to 0.4x10(9)/l approximately 5 weeks later. H&E sections showed a mixed infiltrate of eosinophils and neutrophils extending through the reticular dermis and septa of the panniculus. No deep fascia was obtained on biopsy. The immunohistochemical stain for transforming growth factor beta 1 showed staining of endothelial cells and dendritic cells. The interleukin-5 stain was negative. Our results suggest that quinolinic acid may play a role in cutaneous eosinophilic disorders.

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Possible role of cytokine‐induced tryptophan degradation in anaemia of inflammation

Cited by 50 publications

References 25 publications

Antioxidants, inflammation and cardiovascular disease

Antioxidants, inflammation and cardiovascular disease

Use of dried kapenta (Limnothrissa miodon and Stolothrissa tanganicae) and other products based on whole fish for complementing maize-based diets

Is the L-tryptophan metabolite quinolinic acid responsible for eosinophilic fasciitis?

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