Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized by increased expression of type I interferons (IFNs). Indoleamine 2,3-dioxygenase (IDO), a type I IFN-regulated protein, limits the conversion of tryptophan to serotonin in favor of kynurenine. Serotonin has been implicated in development of cardiovascular disease in the general population, but its role in SLE, a disease characterized with markedly increased cardiovascular morbidity and mortality, is not known. The aim of this study was to investigate if SLE patients had a type I IFN-mediated dysregulation of the serotonin production and whether or not this was associated to cardiovascular disease.

Methods: Serotonin was measured in serum from patients with SLE (n=148) and healthy volunteers (n=79) with ELISA and intracellularly in platelets using flow cytometry and related to cardiovascular disease adjusted for traditional risk factors. Tryptophan and kynurenine were measured by liquid chromatography.

Results: SLE patients had decreased serum and platelet levels of serotonin as compared to healthy volunteers. The serum levels were associated to type I IFNs, compatible with IFN-mediated skewing of the tryptophan metabolism. Serum serotonin levels were inversely associated to disease severity and cardiovascular disease in SLE patients, independently of traditional cardiovascular risk factors.

Conclusion:

We suggest that the serotonin system is dysregulated in SLE due to increased type I IFN production. Furthermore, the serum level of serotonin is identified as a novel risk factor for cardiovascular disease in SLE, independently of traditional cardiovascular risk factors.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/type-i-interferon-mediated-skewing-of-the-serotonin-synthesis-in-systemic-lupus-erythematosus-is-associated-to-cardiovascular-disease/