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 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.
Filaci
G
G
Department of Internal Medicine, University of Genoa, Italy.
Pelli
N
N
Sacco
T
T
Contini
P
P
Lanza
L
L
Picciotto
A
A
Scudeletti
M
M
Puppo
F
F
Castiglioni
G
G
Indiveri
F
F
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*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D002635:Chenodeoxycholic Acid; D012436:S-Adenosylmethionine; D007371:Interferon-gamma