Patients suffering from autoimmune disease, cancer or chronic inflammatory diseases mostly suffer from severe “complications” of their underlying illness, like weight loss, physical inefficiency, immunodeficiency, anemia, chronic fatigue, mood disorders or even depression. All these symptoms can severely impair the quality of life of patients. The percentage of patients with chronic diseases complaining about poor quality of life is high, irrespective of their underlying disease.
Interestingly, most patients suffering from chronic inflammatory disease have a strongly disturbed tryptophan metabolism. Within cellular immune response the essential amino acid tryptophan is degraded by the enzyme indoleamine-2,3-dioxygenase (IDO), leading to lowered tryptophan serum/plasma concentrations and increased levels of tryptophan catabolites like kynurenine. Tryptophan is not only necessary for the growth and proliferation of various cells as well as pathogens, it is also the precursor of the important neurotransmitters serotonin (5-hydroxytryptamin) and nicotinamide adenine dinucleotide (NAD). Increased tryptophan degradation within chronic inflammatory cascades thus leads to a diminished tryptophan availability, which might not only decrease the immunoresponsiveness of patients, but may also influence their mood, physical strength and haematopoiesis.
In fact, immune-mediated tryptophan degradation is supposed to contribute importantly to the development of fatigue, weight loss, and neuropsychiatric disorders. This review provides an overview, how enhanced IDO-activation might contribute to the development of various symptoms impairing the quality of life of patients with chronic disease.
Brandacher G, Amberger A, Schroecksnadel K, Margreiter R, Fuchs D. (2007). Predictive value of IFN-g induced Indoleamine 2,3-dioxygenase (IDO) expression in cancer patients. Cancer Management in Man.Google Scholar
Brown BR, Baranowski MD, Kulig JW, Stephenson JN, Perry B. (1996). Adolescence. 31: 253–264.PubMedGoogle Scholar
Brown RR, Ozaki Y, Datta SP, Borden EC, Sondel PM, Malone DG. (1991). Adv Exp Med Biol. 294: 425–435.PubMedGoogle Scholar
Grohmann U, Fallarino F, Bianchi R, Vacca C, Orabona C, Belladonna ML, Fioretti MC, Puccetti P. (2003). Adv Exp Med Biol. 527: 47–54.PubMedGoogle Scholar
Holzner B, Kemmler G, Greil R, Kopp M, Zeimet A, Raderer M, Hejna M, Zochbauer S, Krajnik G, Huber H, Fleischhacker WW, Sperner-Unterweger B. (2002). Ann Oncol. 13: 965–973.PubMedCrossRefGoogle Scholar