Immunosuppressive effects of the S-adenosylhomocysteine hydrolase inhibitor, 3-deazaadenosine.
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.
D043383:Adenosylhomocysteinase; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D006710:Homocysteine / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D012263:Ribonucleosides / Q000494:pharmacology*; D012756:Sheep; D014372:Tubercidin / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C018258:3-deazaadenosine; D006710:Homocysteine; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D014372:Tubercidin