Increased interferon-mediated immunity following in vitro and in vivo Modafinil treatment on peripheral immune cells

Author(s):Show less -

Zager, Adriano ^{[1, 2]} ; Brandao, Wesley Nogueira ^[3] ; Margatho, Rafael Oliveira ^[1] ; Gimenes Cruz, Daniel Sanzio ^[1] ; Peron, Jean Pierre ^[3] ; Tufik, Sergio ^[4] ; Andersen, Monica Levy ^[4] ; Moresco, Monica ^[5] ; Pizza, Fabio ^{[5, 6]} ; Plazzi, Giuseppe ^{[5, 6]} ; Kornum, Birgitte Rahbek ^[2] ; Palermo-Neto, Joao ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Neuroimmunomodulat Res Grp, Sao Paulo - Brazil

^[2] Rigshosp, Mol Sleep Lab, Dept Clin Biochem, Glostrup Res Inst, Glostrup - Denmark

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmune Interact Lab, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, UNIFESP, EPM, Dept Psychobiol, Sao Paulo - Brazil

^[5] Univ Bologna, Dept Biomed & Neuromotor Sci DIBINEM, Bologna - Italy

^[6] ASL Bologna, IRCCS, Inst Neurol Sci, Bologna - Italy

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 81, p. 297-305, FEB 2 2018.
• Web of Science Citations: 2

Abstract

The wake-promoting drug Modafinil has been used for treatment of sleep disorders, such as Narcolepsy, excessive daytime sleepiness and sleep apnea, due to its stimulant action. Despite the known effect of Modafinil on brain neurochemistry, particularly on brain dopamine system, recent evidence support an immunomodulatory role for Modafinil treatment in neuroinflammatory models. Here, we aimed to study the effects of in vitro and in vivo Modafinil treatment on activation, proliferation, cell viability, and cytokine production by immune cells in splenocytes culture from mice. The results show that in vitro treatment with Modafinil increased Interferon (IFN)-gamma, Interleukin (IL)-2 and IL-17 production and CD25 expression by T cells. In turn, in vivo Modafinil treatment enhanced splenocyte production of IFN-gamma, IL-6 and tumor necrosis factor (TNF), and increased the number of IFN-gamma producing cells. Next, we addressed the translational value of the observed effects by testing PBMCs from Narcolepsy type 1 patients that underwent Modafinil treatment. We reported increased number of IFN-gamma producing cells in PBMCs from Narcolepsy type 1 patients following continuous Modafinil treatment, corroborating our animal data. Taken together, our results show, for the first time, a pro-inflammatory action of Modafinil, particularly on IFN-mediated immunity, in mice and in patients with Narcolepsy type 1. The study suggests a novel effect of this drug treatment, which should be taken into consideration when given concomitantly with an ongoing inflammatory or autoimmune process. (AU)

• FAPESP's process: 15/18803-8 - Effects of pharmacological treatment with modafinil on T cell response of patients with type 1 narcolepsy
• Grantee: Adriano Zager
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 09/51886-3 - Neuroimmunomodulation: drugs, stress and cytokines on nervous, endocrine and immune systems relationships
• Grantee: João Palermo Neto
• Support type: 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 type: Scholarships in Brazil - Post-Doctorate