Effects of 1-Methyltryptophan on Immune Responses and the Kynurenine Pathway after Lipopolysaccharide Challenge in Pigs

International Journal of Molecular Sciences

Elisa Wirthgen¹  Margret Tuchscherer¹  Winfried Otten¹  Ellen Kanitz¹  Armin Tuchscherer²  Juliane Günther³  Julia Brenmoehl³  Daniela Ohde³  Grazyna Domanska⁴  Eberhard Scheuch⁵  Werner Weitschies⁶  Anne Seidlitz⁶ 

[1] Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), D-18196 Dummerstorf, Germany;Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), D-18196 Dummerstorf, Germany;Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), D-18196 Dummerstorf, Germany;Institute of Immunology and Transfusion Medicine, University of Greifswald, D-17475 Greifswald, Germany;Institute of Pharmacology, University of Greifswald, D-17489 Greifswald, Germany;Institute of Pharmacy, University of Greifswald, D-17489 Greifswald, Germany;

关键词: indoleamine 2,3-dioxygenase;    kynurenine pathway;    methyltryptophan;    LPS;    pig;   

DOI  :  10.3390/ijms19103009

来源: DOAJ

【 摘 要 】

An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT) is currently in the interest of research due to its potential inhibitory effects on IDO1 and immunomodulatory properties. The present study aims to investigate the protective and immunomodulatory effects of 1-methyltryptophan against endotoxin-induced shock in a porcine in vivo model. Effects of 1-MT were determined on lipopolysaccharide (LPS)-induced tryptophan (TRP) degradation, immune response and sickness behaviour. 1-MT increased TRP and its metabolite kynurenic acid (KYNA) in plasma and tissues, suppressed the LPS-induced maturation of neutrophils and increased inactivity of the animals. 1-MT did not inhibit the LPS-induced degradation of TRP to kynurenine (KYN)—a marker for IDO1 activity—although the increase in KYNA indicates that degradation to one branch of the KYN pathway is facilitated. In conclusion, our findings provide no evidence for IDO1 inhibition but reveal the side effects of 1-MT that may result from the proven interference of KYNA and 1-MT with aryl hydrocarbon receptor signalling. These effects should be considered for therapeutic applications of 1-MT.

【 授权许可】

Unknown