S-ADENOSIL-L-METHIONINE IS ABLE TO REVERSE THE IMMUNOSUPPRESSIVE EFFECTS OF CHENODEOXYCHOLIC ACID IN-VITRO

The study was conceived to evaluate if S-adenosil-L-methionine, a subs tance commonly used in the treatment of cholestasis in patients with c irrhosis and chronic hepatitis, exerts any immunological effect and if it is able to counterbalance bile acid-mediated immunosuppression. Pr oliferation and interleukin 2 and interferon-gamma secretion of human lymphocytes, collected from healthy subjects, and exposed to mitogenic stimuli (phytohemagglutinin, pokeweed and anti-CD3 monoclonal antibod ies), were analysed in the basal condition or after exposure to S-aden osil-L-methionine and/or chenodeoxycholic acid. Chenodeoxycholic acid inhibited phytohemagglutinin-induced lymphocyte proliferation and inte rferon-gamma secretion, and phytohemagglutinin and pokeweed-mediated i nterleukin 2 secretion. S-adenosil-L-methionine did not affect lymphoc yte proliferation while it reduced interleukin 2 secretion upon phytoh emagglutinin and pokeweed stimulation and interferon-gamma secretion u pon all stimuli tested. Moreover, S-adenosil-L-methionine counteracted chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion. The results of our study confirm the imm unosuppressive role of chenodeoxycholic acid on both secretive and pro liferative lymphocyte functions and provide evidence of immunomodulato ry activities of S-adenosil-L-methionine and its capacity to antagoniz e chenodeoxycholic acid-mediated inhibition of lymphocyte proliferatio n and interleukin 2 secretion. (C) 1997 International Society for Immu nopharmacology.