title: S-adenosil-L-methionine is able to reverse the immunosuppressive effects of chenodeoxycholic acid in vitro.
abstract: The study was conceived to evaluate if S-adenosil-L-methionine, a substance commonly used in the treatment of cholestasis in patients with cirrhosis and chronic hepatitis, exerts any immunological effect and of it is able to counterbalance bile acid-mediated immunosuppression. Proliferation 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 antibodies), were analysed in the basal condition or after exposure to S-adenosil-L-methionine and/or chenodeoxycholic acid. Chenodeoxycholic acid inhibited phytohemagglutinin-induced lymphocyte proliferation and interferon-gamma secretion, and phytohemagglutinin and pokeweed-mediated interleukin 2 secretion. S-adenosil-L-methionine did not affect lymphocyte proliferation while it reduced interleukin 2 secretion upon phytohemagglutinin and pokeweed stimulation and interferon-gamma secretion upon 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 immunosuppressive role of chenodeoxycholic acid on both secretive and proliferative lymphocyte functions and provide evidence of immunomodulatory activities of S-adenosil-L-methionine and its capacity to antagonize chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion.
authors.affiliation: Department of Internal Medicine, University of Genoa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Filaci
authors.forename: N
authors.initials: N
authors.lastname: Pelli
authors.forename: T
authors.initials: T
authors.lastname: Sacco
authors.forename: P
authors.initials: P
authors.lastname: Contini
authors.forename: L
authors.initials: L
authors.lastname: Lanza
authors.forename: A
authors.initials: A
authors.lastname: Picciotto
authors.forename: M
authors.initials: M
authors.lastname: Scudeletti
authors.forename: F
authors.initials: F
authors.lastname: Puppo
authors.forename: G
authors.initials: G
authors.lastname: Castiglioni
authors.forename: F
authors.initials: F
authors.lastname: Indiveri
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002635:Chenodeoxycholic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D002635:Chenodeoxycholic Acid; D012436:S-Adenosylmethionine; D007371:Interferon-gamma