Endocannabinoids suppress inflammation-induced tumor necrosis factor alpha up-regulation in human and Guinea-pig lungs

<bold>Background:</bold> Endocannabinoids (ECs) exhibit therapeutic potential in lipopolysaccharide (LPS)-induced and allergic airway inflammation (Abohalaka et al. Pulmonary pharmacology & therapeutics. 2020: 101920.), however, their mechanism remain partially understood. <bold>Aims:</bold> To examine the effect of the endogenous and exogenous cannabinoids on inflammation-induced TNF-α production in the airways. <bold>Methods:</bold> Guinea pig (n=4) and human (n=3) lung tissues were incubated by LPS (1uM/ml) or monoacylglycerol lipase (MAGL) inhibitor JZL184 (1uM/ml), fatty acid amide hydrolase (FAAH) inhibitor URB597 (1uM/ml), MAGL/FAAH dual inhibitor JZL195 (1uM/ml), 2-arachidonoylglycerol (30uM/ml), anandamide (30uM/ml), oleoylethanolamide (10uM/ml), cannabinoid receptor CB1 antagonist AM281 (10uM/ml), CB2 agonist JWH133 (10uM/ml), and dexamethasone (0.1uM/ml) in the presence of LPS in a culture medium. TNF-α levels in the culture media were quantified by ELISA afterwards. <bold>Results:</bold> Exogeneous cannabinoids or the inhibition of EC metabolism demonstrated a suppression of TNF-α production in both human and Guinea pig lungs (Figure 1). <bold>Conclusions:</bold> ECs demonstrate a suppressive effect on TNF-α production induced by LPS exposure, acting through CB2 receptors in both human and Guinea pig models. Concurrent administration of ECs and an inhibitor of EC metabolism tends to elicit an enhanced effect when compared to single treatments. <fig><object-id>erj;64/suppl_68/PA2986/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>