Possible Interaction: Interferons and Tryptophan

“It has also been reported that SCFAs and tryptophan metabolites can reduce proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interferon-γ and promote the anti-inflammatory cytokines, all of which are vital mediators of radiation-induced damage.”

“The pro-inflammatory cytokine IFN-γ suppresses growth and differentiation of erythroid progenitor cells, and the depletion of TRP limits protein synthesis and thus hemoglobin production, and, through reduction in oxygen supply, may contribute to ischemic vascular disease.”

“Exposure of various cell types to IFN results in increased enzymatic activities leading to the breakdown of tryptophan and evidence exists to suggest that the catabolism of tryptophan may be connected to the biological effects of interferon (Carlin et al., 1989.”

“ INFs are known to shift the metabolism of tryptophan (TRP) away from its role as a precursor of serotonin.”

“Direct interactions between quinolines and the oxygenases of the pathway (especially with … indoleamine (2,3)-dioxygenase and kynurenine-monoxygenase) and indirect influences via the interferon-γ induced … of tryptophane are discussed, as well as the modifying effect of the already existing neurotoxicity of the single quinoline related drug used.”

“Its synthesis from tryptophan is stimulated by interferon γ and may represent an important compensatory pathway for the regulation of vascular function in inflammatory conditions.”

“The molecular mechanism(s) underlying this finding is still unknown but it has been suggested that HCV and/or interferon administration may increase indoleamine 2,3-dioxygenase (IDO) activity, and reduce plasma tryptophan (TRP) levels and brain serotonin synthesis thus leading to psychopathological disorders.”

“Moreover interferon induces the activity of 2, 3 indoloamine dioxygenase, the enzyme which converts tryptophan into kynurenine, leads to a reduced level of tryptophan , and thus to a reduced level of central serotonin and to an increased level of neurotoxic kynurenine metabolites.”

“ Interferon substantially induced indoleamine 2,3-dioxygenase and increased L-tryptophan metabolism in human peripheral blood monocytes.”

“Moreover, tryptophan reduced the expression of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, interferon (IFN)-gamma, IL-12p40, IL-1beta and IL-17, as well as IL-8 and intracellular adhesion molecule-1, and resulted in increased expression of apoptosis initiators caspase-8 and Bax.”