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.