Metabolism of the
essential amino acid tryptophan (trp) is a key endogenous immunosuppressive pathway restricting inflammatory responses.
Tryptophan metabolites promote regulatory T cell (Treg) differentiation and suppress proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that treatment with natural and synthetic
tryptophan metabolites can suppress autoimmune
neuroinflammation in preclinical animal models. Here, we tested if oral intake of
tryptophan would increase immunosuppressive
tryptophan metabolites and ameliorate autoimmune
neuroinflammation as a safe approach to treat autoimmune disorders like
multiple sclerosis (MS). Without oral supplementation, systemic
kynurenine levels decrease during the initiation phase of
experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, indicating systemic activation of
tryptophan metabolism. Daily oral gavage of up to 10 mg/mouse/day was safe and increased serum
kynurenine levels by more than 20-fold for more than 3 h after the gavage. While this treatment resulted in suppression of myelin-specific Th1 responses, there was no relevant impact on clinical disease activity. These data show that oral trp supplementation at subtoxic concentrations suppresses
antigen-specific Th1 responses, but suggest that the increase in trp metabolites is not sustained enough to impact
neuroinflammation.