The Role of Kynurenines Produced by Indolamine-2,3-Dioxygenase 1 in Sepsis.

Lerch, Simon; Schefold, Joerg C; Spinetti, Thibaud (2022). The Role of Kynurenines Produced by Indolamine-2,3-Dioxygenase 1 in Sepsis. Pharmacology, 107(7-8), pp. 359-367. Karger 10.1159/000523965

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BACKGROUND

The enzyme indolamine-2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme of the kynurenine (KYN) pathway and metabolizes the essential amino acid tryptophan to KYNs. The depletion of tryptophan and the generation of KYNs were shown to be involved in the global downregulation of the immune system during the later stages of sepsis, also referred to as sepsis-associated immunosuppression.

SUMMARY

The generation of KYNs by IDO1 leads to a depletion of effector T cells, including increased rate of apoptosis, decreased ability of T-cell proliferation and activation, and the generation of FoxP3+ regulatory T cells. Furthermore, KYN was shown a potent vasorelaxant during inflammation-induced hypotension. Experimental studies in murine sepsis models and in humans show promising data for using the activation of IDO1 both as a prognostic marker and potential drug target in sepsis.

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