Inflammation Suppresses an Endocannabinoid-Degrading Enzyme, Possibly to Self-Limit
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Inflammation suppressed Ces2g, reducing 2-AG breakdown in the spleen
- Evidence Grade:
- Well-designed animal study with multiple confirmation approaches, but the effect was modest and the clinical significance requires further investigation.
- Study Age:
- Published in 2015. Endocannabinoid-immune system interactions remain an active research area.
- Original Title:
- Lipopolysaccharide suppresses carboxylesterase 2g activity and 2-arachidonoylglycerol hydrolysis: A possible mechanism to regulate inflammation.
- Published In:
- Prostaglandins & other lipid mediators, 121(Pt B), 199-206 (2015)
- Authors:
- Szafran, Brittany, Borazjani, Abdolsamad, Lee, Jung Hwa, Ross, Matthew K, Kaplan, Barbara L F
- Database ID:
- RTHC-01065
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Does the body use endocannabinoids to fight inflammation?
This study suggests yes. When inflammation was triggered, the spleen reduced its breakdown of the endocannabinoid 2-AG, effectively boosting anti-inflammatory endocannabinoid signaling. This appears to be a natural self-limiting mechanism.
Could this explain why cannabis reduces inflammation?
Partially. Cannabis introduces external cannabinoids that mimic or enhance what the body is already trying to do naturally. This study shows the body has a built-in mechanism to boost endocannabinoid signaling during inflammation, and cannabis use would amplify this effect.
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Cite This Study
https://rethinkthc.com/research/RTHC-01065APA
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
MLA
Szafran, Brittany, et al. "Lipopolysaccharide suppresses carboxylesterase 2g activity and 2-arachidonoylglycerol hydrolysis: A possible mechanism to regulate inflammation.." Prostaglandins & other lipid mediators, 2015. https://doi.org/10.1016/j.prostaglandins.2015.09.005
RethinkTHC
RethinkTHC Research Database. "Lipopolysaccharide suppresses carboxylesterase 2g activity a..." RTHC-01065. Retrieved from https://rethinkthc.com/research/szafran-2015-lipopolysaccharide-suppresses-carboxylesterase-2g
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.