In vivo modulation of LPS-induced alterations in brain and peripheral cytokines and HPA axis activity by cannabinoids.
This study investigated cannabinoid receptor-mediated regulation of brain and peripheral cytokines in vivo. The cannabinoid receptor agonist, HU210 attenuated lipopolysaccharide (LPS)-induced increases in IL-1beta and TNFalpha in rat brain and IL-1beta, TNFalpha, IL-6 and IFNgamma in plasma. The CB(1) receptor antagonist, SR141716A, attenuated the immunosupressive effects of HU210 on IL-1beta, but not TNFalpha. SR141716A or the CB(2) receptor antagonist, SR144528, alone attenuated LPS-induced cytokine increases. LPS and/or cannabinoids also reduced circulating lymphocyte numbers and increased corticosterone levels. These data provide evidence for modulation of pro-inflammatory cytokines in vivo by cannabinoid receptors and inform the development of cannabinoids for neuroinflammatory disorders.
Roche
Michelle
M
Department of Physiology, National University of Ireland, Galway, University Road, Galway, Ireland.
Diamond
Michael
M
Kelly
John P
JP
Finn
David P
DP
D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000276:immunology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001892:Camphanes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; C110630:SR 144528; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013759:Dronabinol; D007371:Interferon-gamma; C062018:HU 211; D000077285:Rimonabant; D003345:Corticosterone