Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines

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Tauil, Carlos B. ; Lima, Amanda D. da Rocha ; Ferrari, Breno B. ; da Silva, Veronica A. G. ; Moraes, Adriel S. ; da Silva, Flavia M. ; Melo-Silva, Cesar A. ; Farias, Alessandro S. ; Branda, Carlos O. ; Leonilda, M. B. dosSantos ; dos Santos-Neto, Leopoldo L.

• Document type: Journal article
• Source: BRAIN, BEHAVIOR, & IMMUNITY - HEALTH; v. 9, p. 7-pg., 2020-12-01.

Abstract

Depression/anxiety (D/A) occurs in up to 50% of multiple sclerosis (MS) patients. Proinflammatory cytokines induce classical symptoms of depression. Activation of the inflammatory response also triggers production of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, the amino acid precursor of serotonin and melatonin. It has been suggested that IDO is the link between the immune and serotonergic systems.This study aimed to quantify the levels of IDO and pro-inflammatory and anti-inflammatory cytokines in patients with MS and depression, according to treatment with interferon-beta (IFN-I3) or fingolimod. The study inclusion criteria were age 18-60 years and a clinical and radiological diagnosis of MS. One hundred and thirtytwo patients diagnosed by McDonald's criteria and followed up at Brasilia District Hospital, Brazil, with relapsingremitting MS were identified as potential study participants. Thirty-five of these patients were identified to be receiving treatment with fingolimod or IFN-I3 and to have a diagnosis of D/A. IDO and pro-inflammatory and antiinflammatory cytokine levels were compared between these 35 patients and 18 healthy controls. The level of IL10 (an anti-inflammatory cytokine) was lower in both the fingolimod-treated (P < 0.001) and IFN-I3-treated (P < 0.01) patient groups than in the control group. IFN-I3-treated patients showed increased IDO expression and decreased inflammatory cytokine levels. In contrast, fingolimod-treated patients showed significantly decreased expression of IDO and significantly increased levels of proinflammatory cytokines produced by innate immune cells, including tumor necrosis factor-alpha and interleukin-6.The agents used to treat MS maintain symptoms of D/A in patients with MS via different mechanisms. (AU)

• FAPESP's process: 14/26431-0 - Multiple sclerosis, clinical study, neuropsychological, immunological, biomarkers and modifying-disease new drugs
• Grantee: Leonilda Maria Barbosa dos Santos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/17404-5 - Study of B lymphocytes subset in peripheral blood of patients with a primary progressive form of multiple sclerosis
• Grantee: Leonilda Maria Barbosa dos Santos
• Support Opportunities: Regular Research Grants