Therapeutic treatment with Modafinil decreases the severity of experimental autoimmune encephalomyelitis in mice

Author(s)

Brandao, Wesley Nogueira ^[1] ; Andersen, Monica Levy ^[2] ; Palermo-Neto, Joao ^[3] ; Peron, Jean Pierre ^[1] ; Zager, Adriano ^{[3, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmune Interact Lab, Sao Paulo - Brazil

^[2] Fed Univ Sao Paulo UNIFESP EPM, Dept Psychobiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Neuroimmunomodulat Res Grp, Sao Paulo - Brazil

^[4] Linkoping Univ, Fac Med & Hlth Sci, Dept Clin & Expt Med, Div Neurobiol, S-58185 Linkoping - Sweden

• Document type: Journal article
• Source: International Immunopharmacology; v. 75, OCT 2019.
• Web of Science Citations: 0

Abstract

The psychostimulant drug modafinil has been used for many years for the treatment of sleep disorders. Recent studies have indicated that modafinil has immunomodulatory properties in the central nervous system (CNS) and peripheral immune cells. Thus, our aim was to determine the effects of in vivo therapeutic treatment with modafinil on the severity of clinical symptoms and immune response during the acute phase of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis. Modafinil treatment, given after the onset of symptoms, resulted in an improvement of EAE symptoms and motor impairment, which was correlated with reduced cellular infiltrate and a decreased percentage of T helper (Th) 1 cells in the CNS. The spinal cord analysis revealed that modafinil treatment decreased interferon (IFN)-y and interleukin (IL)-6 protein levels and down regulated genes related to Th1 immunity, such as IFN-gamma and TBX21, without affecting Th17-related genes. Our research indicates that therapeutic modafinil treatment has anti-inflammatory properties in an EAE model by inhibiting brain Th1 response, and may be useful as adjuvant treatment for multiple sclerosis. (AU)

• FAPESP's process: 17/26170-0 - Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/18921-5 - Effects of modafinil on immunity, neuroinflammation and development of experimental autoimmune encephalomyelitis in mice
• Grantee: Adriano Zager
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/18703-2 - The role of Indoleamine-2,3-dioxigenase and the Triptophan - Kynurenines axis through NMDA receptors over the immune response in the EAE and stroke model
• Grantee: Jean Pierre Schatzmann Peron
• Support Opportunities: Research Grants - Young Investigators Grants