Cannabinoid system and neuroinflammation: implications for multiple sclerosis.
There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in central nervous system inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have potentiated the interest in cannabinoids as potential therapeutic targets. Here our aim was to update the actions of cannabinoids on immune system and glial cells and their implications on multiple sclerosis. We also show our results on the modulation of cytokines of the IL-12 family by cannabinoids in macrophages and brain microglia. We used murine primary cultures of macrophage and microglia activated by lipopolysaccharide/IFN-gamma and Theiler's virus to study the effects of cannabinoids on the regulation of IL-12 and IL-23 mRNA and protein IL-12p40, evaluated by RT-PCR and ELISA, respectively. Cannabinoids negatively regulate the production of these cytokines by microglial cells in part due to the activation of CB(2) receptors. The effects of cannabinoids on cytokine brain work and on the regulation of neuroinflammatory processes may affect chronic inflammatory demyelinating diseases such as multiple sclerosis.
Correa
Fernando
F
Neuroimmunology Group, Functional and Systems Neurobiology Department, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Docagne
Fabian
F
Mestre
Leyre
L
Loría
Frida
F
Hernangómez
Miriam
M
Borrell
José
J
Guaza
Carmen
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D063385:Cannabinoid Receptor Modulators / Q000276:immunology* / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D004660:Encephalitis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D000893:Anti-Inflammatory Agents; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D018664:Interleukin-12