Targeting the Endocannabinoid System to Treat Sepsis

doi:10.22514/sv81.052013.1

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…More clinically relevant models of sepsis induce abdominal peritonitis through fecal translocation from the intestine [27, 45]. However, controversy still exists on the benefit of the CB 2 pathway in these models [8]. Sepsis pathophysiology is quite complex in clinical settings, with time-dependent changes of the status of the immune system.…”

Section: Discussionmentioning

confidence: 99%

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Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis

Sardinha

Kelly

Zhou

et al. 2014

Mediators of Inflammation

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Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics. The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS) in mice and intestinal microcirculation was assessed through intravital microscopy. We found that HU308 (CB2 receptor agonist) reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice. AM630 (CB2 receptor antagonist) maintained the level of adherent leukocytes induced by LPS but further reduced muscular and mucosal villi FCD. URB597 (FAAH inhibitor) and JZL184 (MAGL inhibitor) both reduced the number of adherent leukocytes in submucosal venules but did not restore the mucosal villi FCD. Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.

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Section: Discussionmentioning

confidence: 99%

“…The endocannabinoid system has recently emerged as a potential target in sepsis treatment [8]. This system is an endogenous signalling system that mediates a variety of physiological functions including modulation of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis

Sardinha

Kelly

Zhou

et al. 2014

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…In contrast, CB2 are localized primarily in immune cells such as lymphocytes, macrophages and neutrophils and are responsible for immunomodulatory effects of cannabinoids. (1,3,4) While THC is a low-efficacy partial agonist of cannabinoid receptors, the synthetic cannabinoids are high-potency full agonists for CB1 receptors. (5) Most synthetic cannabinoids are not currently found using routine toxicology screening as they contain synthetic cannabinoids from different chemical classes.…”

Section: Introductionmentioning

confidence: 99%