Immunosuppressive Effects of the S-Adenosylhomocysteine Hydrolase Inhibitor, 3-Deazaadenosine

Autor: Joseph L. Medzihradsky, Gertrude B. Elion, Gerald Wolberg, Thomas P. Zimmerman
Rok vydání: 1982
Předmět:
Zdroj: Journal of Immunopharmacology. 4:29-41
ISSN: 0163-0571
DOI: 10.3109/08923978209031073
Popis: Immunosuppressive effects of 3-deazaadenosine (3-DAA), an inhibitor of S-adenosylhomocysteine hydrolase, were tested in vivo in immune assays against sheep red blood cells (SRBC), involving serum titrations for hemagglutinins and hemolysins, cellular cytotoxicity tests and the direct plaque-forming cell assay. At daily doses up to 100 mg/kg, the compound was suppressive when injected before antigen and the effect appeared to be dose-dependent (ED50 = 52.6 ± 4.9 mg/kg). When doses of 25 mg/kg of 3-DAA were given before antigen, co-injections of 250 mg/kg of L-homocysteine (L-HC) potentiated the suppressive effect, although L-HC alone was inactive. Daily administration of 100 mg/kg of 3-DAA or 250 mg/kg of L-HC alone was not suppressive when given after the antigen; however, in combination they were able to induce suppression. The possible biochemical mechanisms of the suppression, particularly those involving the inhibition of S-adenosylmethionine-dependent methylation reactions, are discussed.
Databáze: OpenAIRE