Effect of delta-8-tetrahydrocannabinol (Δ 8-THC) in modulating immune response and gut microbial dysbiosis in concanavalin-induced acute liver injury

Abstract Autoimmune hepatitis (AIH) is a serious health problem characterized by cellular infiltration and progressive destruction of the hepatic parenchyma resulting in cirrhosis, liver failure death. In current study, we assessed ameliorative role Δ 8-THC limiting disease severity its regulatory on gut microbiota thereby altering differentiation T cell subsets murine model Concanavalin A-induced hepatitis. AIH was induced C57BL/6 mice ConA (12.5mg/Kg i.v.) treated i.p. with vehicle or 20mg/Kg 8-THC. Interestingly, treatment after challenge led to significantly decreased injury enzymes, alanine aminotransferase (ALT) aspartate (AST) levels than exposed mice. Flow cytometry analysis infiltrating cells revealed reduced expression pro-inflammatory cytokines IL-17A IFNγ elevated immunosuppressive TGF-β1 IL-10 ConA-treated following treatment. More importantly, CD4+ helper from RORγt+ Th 17 T-bet+ Th1 Foxp3+ 16S rRNA sequencing microbiome that ConA+Δ naïve groups had lower abundance bacteria belonging families, Ruminococcaceaeand Lachnospiraceaewhile higher Erysipelotrichaceaecompared ConA+Vehicle group. addition, caused accumulation Peptococcaceaefamily which may be responsible for shift anti-inflammatory immune responses. Our data demonstrate used as therapeutic drug against immune-mediated inflammation Supported part NIH grants P01AT003961, P20GM103641, R01ES030144, R01AI129788, R01AI123947 R01AI160896