Tryptophan in wasting diseases: At the crossing between immune function and behaviour

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 12, Issue 4, 2009, Pages 392-397

  Laviano, Alessandro ^a   Meguid, Michael M ^b   Cascino, Antonia ^a   Molfino, Alessio ^a   Fanelli, Filippo Rossi ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b State University of New York Upstate Medical University: College of Medicine   (United States)

Author keywords

Anorexia; Cachexia; Chronic diseases; Immunosuppression; Indoleamine 2,3 dioxygenase; Tryptophan catabolism

Indexed keywords

ANTIGEN; GAMMA INTERFERON; SEROTONIN; TRYPTOPHAN;

ANOREXIA; BRAIN; CELL PROLIFERATION; DEPRESSION; FEEDING BEHAVIOR; HUMAN; HYPOTHALAMUS; ILLNESS BEHAVIOR; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; INFLAMMATION; NEUROTRANSMISSION; NUTRITIONAL STATUS; OXIDATIVE STRESS; PATHOGENESIS; PATHOLOGY; REVIEW; TRYPTOPHAN METABOLISM; WASTING SYNDROME; WEIGHT REDUCTION;

ANOREXIA; CACHEXIA; HUMANS; IMMUNE TOLERANCE; OXIDATIVE STRESS; TRYPTOPHAN; WASTING SYNDROME;

EID: 68049113588     PISSN: 13631950     EISSN: 14736519     Source Type: Journal    
DOI: 10.1097/MCO.0b013e32832b73af     Document Type: Review

References (34)

1. Fearon KC, Voss AC, Hustead DS, Cancer Cachexia Group. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am J Clin Nutr 2006; 83:1345-1350.
2. Bozzetti F, Mariani L. Defining and classifying cancer cachexia: a proposal by the SCRINIO Working Group. J Parenter Enteral Nutr 2008. [Epub ahead of print] doi: 10.1177/0148607108324874.
3. Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clin Nutr 2008; 27:793-799.
4. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4:762-774.
5. Guijarro A, Laviano A, Meguid MM. Hypothalamic integration of immune function and metabolism [chapter #22]. In: Kalsbeek A, Fliers E, Hofman MA, et al., editors. 'Hypothalamic integration of energy metabolism': progress in brain research [vol. #153]. Amsterdam, NL: Elsevier; 2006. pp. 367-405.
6. Laviano A, Inui A, Marks DL, et al. Neural control of the anorexiacachexia syndrome. Am J Physiol Endocrinol Metab 2008; 295:E1000-E1008. A detailed review of the available evidence showing the role of the central and peripheral nervous system in mediating the anorexia-cachexia syndrome.
7. Laviano A, Meguid MM, Preziosa I, Rossi Fanelli F. Oxidative stress and wasting in cancer. Curr Opin Clin Nutr Metab Care 2007; 10:449-456.
8. Ball HJ, Yuasa HJ, Austin CJ, et al. Indoleamine 2,3 dioxygenase-2: a new enzyme in the kynurenine pathway. Int J Biochem Cell Biol 2009; 41:467-471.
9. Lob S, Konigsrainer A, Zieker D, et al. IDO1 and IDO2 are expressed in human tumors: levo-but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother 2009; 58:153-157. An important study analysing IDO1 and IDO2 expression in human cancer cells. Results reveal that human tumours express IDO1 and IDO2, but only IDO1 is responsible for tryptophan degradation.
10. Katz JB, Muller AJ, Prendergast GC. Indoleamine 2,3 dioxygenase in T-cell tolerance and tumoral immune escape. Immunol Rev 2008; 222:206-221. An excellent review addressing the role of IDO in influencing tumoral immune escape. Possible medical applications of the inhibition of this pathway are also discussed.
11. Mantovani A. Inflaming metastasis. Nature 2009; 457:36-37.
12. Utaka S, Avesani CM, Draibe SA, et al. Inflammation is associated with increased energy expenditure in patients with chronic kidney disease. Am J Clin Nutr 2005; 82:801-805.
13. Brandacher G, Winkler C, Schroecksnadel K, et al. Antitumoral activity of interferon-gamma involved in impaired immune function in cancer patients. Curr Drug Metab 2006; 7:599-612.
14. Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998; 281:1191-1193.
15. Mellor AL, Sivakumar J, Chandler P, et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001; 2:64-68.
16. Uyttenhove C, Pilotte L, Theate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoelamine 2,3-dioxygenase. Nat Med 2003; 9:1269-1274.
17. Feder-Mengus C, Wyler S, Hudolin T, et al. High expression of indoleamine 2,3-dioxygenase gene in prostate cancer. Eur J Cancer 2008; 44:2266-2275. By comparing patients with prostate cancer and patients with benign prostatic hyperplasia, the authors demonstrate that IDO expression is more frequently detectable and quantitatively higher in cancer patients.
18. Hoshi M, Ito H, Fujigaki H, et al. Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell leukaemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity. Leuk Res 2009; 33:39-45. This study demonstrates that IDO is highly expressed in acute T-cell leukaemia/ lymphoma cells. More importantly, after chemotherapy, the circulating levels of the catabolites of tryptophan decrease, suggesting that IDO-mediated tryptophan degradation is correlated with tumour mass.
19. Schefold JC, Zeden JP, Fotopoulou C, et al. Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms. Nephrol Dial Transplant 2009. [Epub ahead of print] doi: 10.1093/ndt/gfn739. This study is the first report showing increased IDO activity in patients with chronic kidney disease. An important result of this study is that IDO activity correlates with C-reactive protein levels, suggesting that in chronic kidney disease, induction of IDO may primarily be a consequence of chronic inflammation.
20. Jeong YI, Kim SW, Jung ID, et al. Curcumin suppresses the induction of indoleamine 2,3-dioxygenase by blocking the Janus-activated kinase-protein kinase C(delta)-STAT1 signaling pathway in interferon-(gamma)- stimulated dendritic cells. J Biol Chem 2009; 284:3700-3708. Suppression of IDO activity by curcumin administration reverses IDO-mediated inhibition of T-cell response. Also, the study addresses the interesting topic of the molecular mechanisms responsible for IDO expression by IFN-g.
21. Alamdari N, O'Neal P, Hasselgren PO. Curcumin and muscle wasting: a new role for an old drug. Nutrition 2009; 25:125-129.
22. Lob S, Konigsrainer A, Schafer R, et al. Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells. Blood 2008; 111:2152-2154.
23. Laviano A, Muscaritoli M, Cascino A, et al. Branched-chain amino acids: the best compromise to achieve anabolism? Curr Opin Clin Nutr Metab Care 2005; 8:408-414.
24. Molfino A, Muscaritoli M, Cascino A, et al. Free tryptophan/large neutral amino acid ratios in blood plasma do not predict cerebral spinal fluid concentrations in interleukin-1-induced anorexia. Pharmacol Biochem Behav 2008; 89:31-35. This interesting study investigates the role of acute inflammatory challenges in mediating brain tryptophan accumulation. Results obtained suggest that temporally different mechanisms may be responsible for the entry of tryptophan into the brain, initially mediated by sympathetic activity to ensure a rapid increase of brain tryptophan concentrations. In a later phase, modulation of plasma circulating levels of free tryptophan and its competitors for blood-brain barrier crossing may represent the primary mechanism providing the brain with a constant flux of tryptophan.
25. Molfino A, Rossi Fanelli F, Laviano A. The interaction between pro-inflammatory cytokines and the nervous system. Nat Rev Cancer 2009; 9:224.
26. Tecott LH. Serotonin and the orchestration of energy balance. Cell Metab 2007; 6:352-361.
27. Meguid MM, Fetissov SO, Varma M, et al. Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 2000; 16:843-857.
28. Blaha V, Yang ZJ, Meguid MM, et al. Ventromedial nucleus of hypothalamis is related to the development of cancer induced anorexia: in vivo microdialysis study. Acta Medica (Hradec Kralove) 1998; 41:3-11.
29. Makarenko IG, Meguid MM, Gatto L, et al. Normalization of hypothalamic serotonin (5-HT1B) receptor and NPY in cancer after tumor resection: an immunocytochemical study. Neurosci Lett 2005; 383:322-327.
30. Laviano A, Gleason JR, Meguid MM, et al. Effects of intra-VMN mianserin and IL-1ra on meal number in anorectic tumor-bearing rats. J Investig Med 2000; 48:40-48.
31. Heisler LK, Jobst EE, Sutton GM, et al. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 2006; 51:239-249.
32. Zhou L, Sutton GM, Rochford JJ, et al. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signalling pathways. Cell Metab 2007; 6:398-405.
33. André C, O'Connor JC, Kelley KW, et al. Spatio-temporal differences in the profile of murine brain expression of proinflammatory cytokines and indoleamine 2,3-dioxygenase in response to peripheral lipopolysaccharide administration. J Neuroimmunol 2008; 200:90-99. This important study shows that IDO expression in the brain following peripheral inflammatory challenge occurs in spatially and temporally different waves of activation. This result may explain the sequela of changes in disease-associated changes of behaviour initiated by the development of sickness behaviour followed by depressive-like symptoms.
34. Henry CJ, Huang Y, Wynne A, et al. Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behaviour, and anhedonia. J Neuroinflammation 2008; 5:15. This study provides a solid link between neuroinflammation and changes in behaviour. By reducing neuroinflammation via anti-inflammatory agent, minocycline, IDO expression is reduced, which is paralleled by recovery from sickness behaviour and prevention of anhedonia.