Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats

Brain Res. 2010 Jan 14;1309:116-25. doi: 10.1016/j.brainres.2009.10.054. Epub 2009 Oct 29.

Abstract

Dysfunction of adenosinergic systems has been implicated in the development of multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in animals. Caffeine, a non-selective antagonist of adenosine receptors, has been shown to provide protection against myelin oligodendroglia glycoprotein (MOG)-induced EAE in mice. In this study, we showed that chronic caffeine similarly imparts neuroprotection against EAE induced in rats by guinea pig spinal cord homogenates (GPSCH). GPSCH-induced EAE is characterized by extensive tissue inflammation with a typical chronic disease course. We showed that caffeine decreases the incidence of EAE and attenuates EAE pathology at behavioral, histological (inflammatory cell infiltration and demyelination) and neurochemical (expression of inflammatory cytokines) levels. The attenuation of GPSCH-induced pathology by chronic caffeine treatment was observed at doses of 10 and 30 mg/kg and during both peak and recovery phases of EAE. Furthermore, it was showed that chronic treatment with caffeine up-regulated A1 receptor and TGF-beta mRNAs and suppressed interferon-gamma mRNA in EAE rats. Together with previous reports, our data demonstrates that chronic treatment with caffeine exerts a neuroprotective effect against EAE, possibly through an A(1) receptor-mediated shift from Th1 to Th2 cell function, and provides a neurobiological basis for epidemiological investigation into the possible relationship between caffeine consumption and development of multiple sclerosis in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology*
  • Caffeine / therapeutic use
  • Central Nervous System / drug effects*
  • Central Nervous System / immunology
  • Central Nervous System / physiopathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Administration Schedule
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Guinea Pigs
  • Interferon-gamma / metabolism
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A1 / genetics
  • Receptor, Adenosine A2A / genetics
  • Spinal Cord / chemistry
  • Spinal Cord / immunology
  • Subcellular Fractions
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Cytokines
  • RNA, Messenger
  • Receptor, Adenosine A1
  • Receptor, Adenosine A2A
  • Transforming Growth Factor beta
  • Caffeine
  • Interferon-gamma