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

Figure 4

Enhanced IDO activity and its indicators as potential risk factors for the development of immunoparalysis and poor prognosis in sepsis. Patients with poor outcome have enhanced IDO activity in early state of sepsis leading to increased levels of KYN and KYNA that provokes expression of TGF-β, IL-6, and development of endotoxin tolerance. In ongoing sepsis, IL-6 does not decrease significantly in plasma of nonsurvivors enabling the autocrine activation of IDO via AhR-IL-6-STAT3 loop. The enhanced IDO activity mediates immunosuppressive effects as increased generation of in ongoing sepsis, provoking the establishment of immunoparalysis.