Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis

摘要: The degradation of tryptophan (TRP) along the kynurenine pathway plays a crucial role as neuro- and immunomodulatory mechanism in response to inflammatory stimuli, such lipopolysaccharides (LPS). In endotoxemia or sepsis, an enhanced activation rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO) is associated with higher mortality risk. It assumed that IDO induced immunosuppressive effects provoke development protracted compensatory hypoinflammatory phase up complete paralysis immune system, which characterized by endotoxin tolerance. However, life-threatening immunoparalysis still poorly understood. Recent reports described impact aryl hydrocarbon receptor- (AhR-) mediated pathways on LPS tolerance escape cancer cells. These mechanisms offer new insights for better understanding cellular dysfunctions immunoparalysis. This review provides comprehensive update significant biological functions TRP metabolites complex regulation LPS-induced activation. addition, focuses IDO-AhR-mediated carcinogenesis revealing significance activity establishment sepsis.