Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro

Schizophr Res. 2007 May;92(1-3):108-15. doi: 10.1016/j.schres.2007.01.019. Epub 2007 Mar 23.


Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Blotting, Western
  • Cell Line / cytology
  • Cell Line / drug effects
  • Cell Line / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Haloperidol / pharmacology
  • Interferon-gamma / antagonists & inhibitors*
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / drug effects
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis
  • Mice
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Risperidone / pharmacology*
  • Schizophrenia / drug therapy
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / drug effects


  • Antipsychotic Agents
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Interferon-gamma
  • Haloperidol
  • Risperidone