Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats.
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.
Chen
Guo Qian
GQ
Department of Neurology, the First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang, PR China.
Chen
Yan Yan
YY
Wang
Xin Shi
XS
Wu
Sai Zhen
SZ
Yang
Hui Min
HM
Xu
Hui Qin
HQ
He
Jin Cai
JC
Wang
Xiao Tong
XT
Chen
Jiang Fan
JF
Zheng
Rong Yuan
RY
D000818:Animals; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000235:genetics; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology; D013347:Subcellular Fractions; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D016212:Transforming Growth Factor beta; D002110:Caffeine; D007371:Interferon-gamma