When mice were given a bacterial toxin to trigger inflammation, the enzyme that breaks down 2-AG in the spleen decreased, suggesting the body activates its endocannabinoid system as a natural brake on inflammation.
Read this if you are interested in how the body uses endocannabinoids to naturally control inflammation.
Inflammation suppressed Ces2g, reducing 2-AG breakdown in the spleen
What the researchers found
Researchers hypothesized that inflammation would reduce the activity of enzymes that break down endocannabinoids, thereby boosting anti-inflammatory endocannabinoid levels. They injected mice with the bacterial toxin LPS and measured enzyme activities in brain, liver, and spleen.
Brain and liver enzymes were largely unchanged, but spleen (a key immune organ) showed a modest decrease in carboxylesterase activity and reduced 2-AG hydrolysis at 6 hours post-LPS. This was confirmed in isolated spleen cells treated with LPS.
Proteomic analysis identified carboxylesterase 2g (Ces2g) as the enzyme specifically reduced by inflammation. By decreasing 2-AG breakdown in the spleen, the body may be boosting endocannabinoid signaling through CB2 receptors as a self-limiting mechanism on inflammation.
Why it matters
This study reveals a natural feedback mechanism: inflammation itself triggers the body to reduce endocannabinoid breakdown, potentially as a self-limiting control. This has implications for understanding why cannabis and endocannabinoids modulate immune responses.
The numbers in context
LPS injection caused decreased Ces activity in spleen; decreased 2-AG hydrolysis at 6 hours; brain and liver enzymes unchanged; Ces2g identified as the specific enzyme suppressed
How the study worked
Mouse study using LPS injection to induce inflammation. Activity-based protein profiling (ABPP) of serine hydrolases in brain, liver, and spleen at 6 and 24 hours. 2-AG hydrolase activity assays. ABPP-MudPIT proteomic analysis. Ex vivo splenocyte confirmation.
What this study cannot tell us
Mouse study with acute LPS model that may not reflect chronic inflammation. The decrease in Ces activity was described as "modest." The functional significance of Ces2g-mediated 2-AG hydrolysis relative to MAGL is unclear.
How to read the evidence
Well-designed animal study with multiple confirmation approaches, but the effect was modest and the clinical significance requires further investigation.
When this study was published
Published in 2015. Endocannabinoid-immune system interactions remain an active research area.
The bigger picture
If the endocannabinoid system serves as a natural inflammation brake, chronic conditions that deplete this system could result in unchecked inflammation. This could explain why some chronic inflammatory conditions respond to cannabinoid-based treatments.
Questions still open
- Is this feedback mechanism impaired in chronic inflammatory diseases? Could boosting Ces2g suppression enhance anti-inflammatory responses? Does this mechanism contribute to the anti-inflammatory effects of cannabis?
Common questions
Does the body use endocannabinoids to fight inflammation?
Could this explain why cannabis reduces inflammation?
Read the original research
Lipopolysaccharide suppresses carboxylesterase 2g activity and 2-arachidonoylglycerol hydrolysis: A possible mechanism to regulate inflammation.
Prostaglandins & other lipid mediators, 121(Pt B), 199-206
Citation
Szafran, Brittany; Borazjani, Abdolsamad; Lee, Jung Hwa; Ross, Matthew K; Kaplan, Barbara L F. (2015). Lipopolysaccharide suppresses carboxylesterase 2g activity and 2-arachidonoylglycerol hydrolysis: A possible mechanism to regulate inflammation.. Prostaglandins & other lipid mediators, 121(Pt B), 199-206. https://doi.org/10.1016/j.prostaglandins.2015.09.005
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