Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis

Abstract

BackgroundEvidence is accumulating that a preclinical phase is present before the onset of clinical signs and symptoms of rheumatoid arthritis (RA). This phase represents an important therapeutic window within which interventions can dramatically modulate outcomes. An agent able to prevent RA for high risk individuals in this phase is therefore desired. In this study, we investigated whether tryptophan metabolite, 5-hydroxytryptophan (5-HTP) or 5-methoxytryptophan (5-MTP), can act as such an agent for primary prevention of collagen-induced arthritis (CIA).MethodsMouse splenocytes were pretreated with 5-HTP or 5-MTP and activated by anti-CD3 plus anti-CD28 antibodies in vitro. The percentages of interferon-γ (IFNγ)+CD4+ T cells and interleukin-17 (IL-17)+CD4+ T cells were measured by flow cytometry. The production of pro-inflammatory cytokines, serotonin and kynurenine was measured by enzyme-linked immunosorbent assay. A CIA model was used to investigate the in vivo effects of 5-HTP on the prevention of arthritis.Results5-HTP decreased the percentages of IFNγ+CD4+ T cells and IL-17+CD4+ T cells and suppressed the production of IL-2, IL-4, IL-6, IL-17, tumor necrosis factor-α (TNFα) and IFNγ in activated splenocytes. 5-HTP administered before induction decreased the disease activities in CIA mice and suppressed the production of TNFα, IL-6 and cyclooxygenase-2 in arthritic joints. 5-HTP also increased serotonin, but decreased kynurenine in the CIA mice.Conclusions5-HTP suppresses inflammation and arthritis through decreasing the production of pro-inflammatory mediators. 5-HTP supplement before induction ameliorates arthritis in a CIA model.

The Role of Biogenic Amines in the Regulation of Interaction between the Immune and Nervous Systems in Multiple Sclerosis

“…2 ), suggesting a possible anti-inflammatory effect of SE in MS, which is not associated with cell death and a reduced proliferative response. Similar results were obtained by Yang et al [42] , where treatment of the splenocytes with SE in collagen-induced arthritis decreased the percentage of IL-17-and IFN-γ-producing T cells, and suppressed the production of IL-6, IL-17 and IFN-γ in vitro.…”

Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors

“…Blockade of the AhR in vitro results in attenuation of cytokine production normally induced by pro-inflammatory mediators, such as interleukin-1 and tumor necrosis factor (26). However, AhR are not all created equally with respect to pro-inflammatory potential (27), and 5-hydroxy tryptophan appears to be anti-inflammatory (28), whereas indole itself appears to be pro-inflammatory and is also a particularly strong AhR agonist (29). Thus, it is of interest that patients had lower levels of metabolites that served as cofactors for 5-hydroxy tryptophan synthesis, as well as its downstream products, as well as higher levels of metabolites of kynurenine.…”

Exploring relationships between body condition score, body fat, activity level and inflammatory biomarkers

“…Blood and synovial fluid was centrifuged at room temperature for 15 min at 1610 g . Supernatant was transferred into 1 ml microcentrifuge tubes containing 10 mg indomethacin in DMSO, and frozen at −20°C until analysis for PGE 2 (Enzo PGE 2 ELISA, Cat # ADI‐900‐001) (Yang, Hsu, Meng, & Su, ) and GAG (DMMB binding) (Oke, Hurtig, Keates, Wright, & Lumsden, ; Pearson, Fletcher, & Kott, ). Thawed synovial fluid samples were pretreated with hyaluronidase solution (4 mg/ml; 1:1 v/v) for 30 min prior to analysis, whereas plasma samples were analysed directly.…”