Review: IDO activation, inflammation and musculoskeletal disease, 2019, Ogbechi et al

[Andy]

The IDO/kynurenine pathway is now established as a major regulator of immune system function. The initial enzyme, indoleamine 2,3-dioxygenase (IDO1) is induced by IFNγ, while tryptophan-2,3-dioxygenase (TDO) is induced by corticosteroids. The pathway is therefore positioned to mediate the effects of systemic inflammation or stress-induced steroids on tissue function and its expression increases with age. Disorders of the musculoskeletal system are a common feature of ageing and many of these conditions are characterized by an inflammatory state.

In inflammatory arthritis and related disorders, kynurenine protects against the development of disease, while inhibition or deletion of IDO1 increases its severity. The long-term regulation of autoimmune disorders may be influenced by the epigenetic modulation of kynurenine pathway genes, with recent data suggesting that methylation of IDO may be involved. Osteoporosis is also associated with abnormalities of the kynurenine pathway, reflected in an inversion of the ratio between blood levels of the metabolites anthranilic acid and 3-hydroxy-anthranilic acid. This review discusses evidence to date on the role of the IDO/kynurenine pathway and the highly prevalent age-related disorders of osteoporosis and rheumatoid arthritis and identifies key areas that require further research.

Paywall, https://www.sciencedirect.com/science/article/pii/S0531556519305807
Sci hub, https://sci-hub.se/10.1016/j.exger.2019.110820

 

[Creekside]

>'The initial enzyme, indoleamine 2,3-dioxygenase (IDO1) is induced by IFNγ, while tryptophan-2,3-dioxygenase (TDO) is induced by corticosteroids.'

That's interesting. My ME symptoms were worse during periods when my IFN-g should have been elevated (24 hrs after physical exertion, or viral infections), and were definitely made worse by elevating TRP in my brain. Prednisone gave me temporary remission the first two times (then stopped working). Maybe the prednisone boosted TDO enough to temporarily deplete TRP in my brain, making it unavailable to the IDO pathway, which leads to neurotoxic kynurenines. Not sure how to test that now.