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

Adriano Zager, Wesley Nogueira Brandão, Rafael Oliveira Margatho, Daniel Sanzio Gimenes Cruz, Jean Pierre Peron, Sergio Tufik, Monica Levy Andersen, Monica Moresco, Fabio Pizza, Giuseppe Plazzi, Birgitte Rahbek Kornum, João Palermo-Neto

Research output: Contribution to journalArticlepeer-review

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)-γ, Interleukin (IL)-2 and IL-17 production and CD25 expression by T cells. In turn, in vivo Modafinil treatment enhanced splenocyte production of IFN-γ, IL-6 and tumor necrosis factor (TNF), and increased the number of IFN-γ 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-γ 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.

Original languageEnglish
Pages (from-to)297-305
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume81
DOIs
Publication statusPublished - 2018

Keywords

  • Human
  • Interferon-γ
  • Mice
  • Modafinil
  • Narcolepsy type 1
  • Peripheral immune cells

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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