CQMUH-011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes

CQMUH-011 is a modified adamantane sulfonamide compound, that inhibits macrophage proliferation and possesses anti-inflammatory properties. Here, fresh mouse splenocytes were obtained and stimulated with concanavalin A (ConA, 5 mu g/ml) in vitro; and experimental autoimmune hepatitis (AIH) was induced by ConA (20 mg/kg, iv) in vivo, to clarify the protective effects of CQMUH-011 against AIH and its possible mechanisms. Our results demonstrated that CQMUH-011 pretreatment can dose-dependently inhibit the proliferation of splenocytes in vitro. In vivo, CQMUH-011 administration reduced the hepatic histopathological score and the infiltration of lymphocytes in the liver parenchyma; additionally, it downregulated the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 in serum, as well as those of methane dicarboxylic aldehyde and myeloperoxidase in the liver tissues. It also down-regulated the expression of p-NF-kappa B and related proteins in the liver tissues. Furthermore, CQMUH-011 could maintain the balance of CD3(+)CD4(+)/CD3(+)CD8(+) and decrease the percentages of CD8(+)CD69(+) and CD4(+)CD25(+/-)CD69(+) T-cells in the splenocytes of ConA-challenged mice. Moreover, we found thatCD4(+)CD25(+/-)CD69(+) T-cells were significantly correlated with ALT levels, especially CD4(+)CD25(-)CD69(+) T-cells. In conclusion, CQMUH-011 exerts potential protective effects against ConA-induced hepatitis, which may be partially attributed to its inhibition of T cells, especially the suppression of the proliferation of CD4(+)CD25(-)CD69(+) and CD8(+)CD69(+) subsets in the spleen. CQMUH-011 also reduced the early apoptosis of lymphocytes in the thymus.