Phytosterols ameliorate clinical manifestations and inflammation in experimental autoimmune encephalomyelitis.
BACKGROUND
Using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), the objective of this study was to examine the effect of phytosterol (PS) administration on inflammation-based EAE development.


METHODS
Female SJL mice were orally administered PS prior to disease induction and maintained throughout the experiment. EAE was induced with antigenic peptide (PLP(131-155)). Mice were clinically scored for disease and euthanized for biochemical and histological analysis of inflammation.


RESULTS
PS delayed onset of EAE development by 2 days and decreased disease severity by 55%. Brain histological analysis revealed an 82% decrease in central nervous system (CNS) inflammatory infiltration and a 48% decrease in demyelination in PS-treated mice versus control. Immunohistochemistry (IHC) showed a 35% reduction in macrophages entering brains of PS-treated mice. Anti-inflammatory interleukin (IL)-10 was up-regulated by 10%, while pro-inflammatory CCL2 was inhibited by 50% with PS treatment. Additionally, PS slightly decreased other pro-inflammatory factors, such as tumor necrosis factor (TNF)-α, IL-6, and interferon (IFN)-γ.


CONCLUSIONS
PS protects against development of EAE by reducing infiltration and inflammatory activity of immune cells into CNS of treated mice, thereby decreasing demyelination associated with EAE. These results provide evidence to support PS as a preventative agent that helps to protect against the development of inflammation-driven disease, such as MS.
SUNY at Buffalo, 2 Sherman Hall, Buffalo, NY 14214, USA.
Michael
M
Valerio
Hong-Biao
HB
Liu
Reid
R
Heffner
Robert
R
Zivadinov
Murali
M
Ramanathan
Bianca
B
Weinstock-Guttman
Atif B
AB
Awad
D000821:Animal Feed; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002490:Central Nervous System / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000188:drug therapy*; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D010840:Phytosterols / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D010455:Peptides; D010840:Phytosterols