Immunomodulation of microglia by docosahexaenoic acid and eicosapentaenoic acid.
OBJECTIVE
The omega-3 fatty acids (ω-3 FAs) docosahexaenoic acid and eicosapentaenoic acid are dietary components which have been ascribed many different health benefits. Inflammation is present in, and contributes to, pathological conditions in the central nervous system (CNS). Microglia are the primary cells with immune function in the CNS, and inflammation mediated by activated microglia is present in pathological conditions. In this review, we present and discuss findings on the modulation of microglial activities by ω-3 FAs in vivo as well as in vitro, and propose mechanisms for their effects.


RESULTS
The majority of studies show that ω-3 FAs have anti-inflammatory effects on microglia. However, phagocytosis is an activity associated with inflammation and is increased by ω-3 FAs. This can be understood in the light of recent research on the resolution of inflammation. Resolution is induced by proresolving factors, which are metabolites of ω-3 FAs. Proresolving factors are anti-inflammatory and have been shown to increase phagocytosis. Other mechanisms of the anti-inflammatory actions of ω-3 FAs involve the peroxisome proliferator-activated receptor-γ, ω-3 FA incorporation into the cell membrane, and inhibition of ion currents.


CONCLUSIONS
Immunomodulation by ω-3 FAs is mediated by several pathways that are interconnected and is a potential therapy for disorders in the CNS.
Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. Erik.Hjorth@ki.se
Erik
E
Hjorth
Yvonne
Y
Freund-Levi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D023421:Models, Animal; D010587:Phagocytosis / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid