Bypassing a relatively common deficiency in neurotransmitter synthesis blocks allergic inflammation (97.8)

Abstract

Abstract An unaddressed triad of symptoms in allergic patients includes: 1) allergic/asthmatic responses, 2) anxiety/depression, and 3) constipation/acid reflux. We proposed that there is a common mediator of these symptoms. It is reported that a deficiency in the neurotransmitter serotonin increases anxiety/depression and reduces peristaltic gastrointestinal movement. In addition, leukocytes synthesize serotonin and serotonin receptors are on leukocytes. Therefore, we proposed that a common mediator is a deficiency in synthesis of the serotonin precursor, 5-hydroxytryptophan (5HTP). A reduction in synthesis of 5HTP occurs due to common polymorphisms in the rate limiting enzyme tryptophan hydroxylase (TPH). TPH converts tryptophan to 5HTP and decarboxylases convert 5HTP to serotonin. To address 5HTP regulation of inflammation, we determined whether dietary supplementation with 5HTP reduces mouse allergic lung inflammation induced by OVA or by house dust mite (DerP1). C57BL/6 mice were used since they have some of the serotonin pathway polymorphisms. 5HTP-containing diets were started two days before antigen. Interestingly, 5HTP blocked lung inflammation 50-70% without affecting body weight, blood eosinophils, Th1/Th2 cytokines, or chemokines. In addition, 5HTP pretreatment of endothelial cells blocked leukocyte transendothelial migration, suggesting that leukocyte recruitment is inhibited. Thus, 5HTP and its metabolites are critical for regulation of allergic inflammation.