Immunostimulatory properties of ethylene-2,2' -bis(dithio)bis(ethanol) and related compounds in vivo.
ADA 202-718, as well as HEDS and higher homologues of ADA 202-718, were found to profoundly stimulate the delayed type hypersensitivity reaction in mice when given i.p. or orally in a dose range of 0.1 - 10 mg/kg. While even a single application of ADA 202-718 at the time of sensitization resulted in a stimulation of the hypersensitivity reaction, administration of the compound at the time of challenge was without effect. When ADA 202-718 was given to animals which were subjected to immunosuppressive therapy by cyclosporine, the suppressed hypersensitivity reaction was restored to normal. At much higher doses (50-200 mg/kg) ADA 202-718 enhanced the local graft-vs-host reaction in the rat. ADA 202-718 did not interfere with the suppressed graft-vs-host reaction obtained by immunosuppressive treatment with cyclosporine nor with the immunosuppressed skin transplant rejection. Single applications of HEDS or ADA 202-718 enhanced the humoral response of mice to sheep erythrocytes as well as to haptenized sheep or chicken erythrocytes. Although antibody levels at the time of maximal antibody production (day 4 for IgM) were only moderately enhanced, elevated antibody titres (IgM and IgG) were found even 23 days after sensitization. The age-dependent decreased humoral response of mice to sheep erythrocytes tended to be partially restored by twice weekly oral applications of HEDS or ADA 202-718 (0.1 to 1 mg/kg for 4 weeks). ADA 202-718 did not decrease the swelling in the Freund's adjuvant induced arthritis in the rat, but reduced the pain in this model. Swelling in a locally induced oedema was reduced in a dose-independent fashion. ADA 202-718 was more effective than acetyl salicylic acid in alleviating the oedema-associated pain.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy; D003524:Cyclosporins / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D000431:Ethanol / Q000031:analogs & derivatives*; D005260:Female; D006087:Graft vs Host Reaction / Q000187:drug effects; D006462:Hemolytic Plaque Technique; D006968:Hypersensitivity, Delayed; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D011917:Rats, Inbred Lew; D016038:Skin Transplantation
D000276:Adjuvants, Immunologic; D003524:Cyclosporins; D004220:Disulfides; D000431:Ethanol; C031319:2-hydroxyethyl disulfide; C045470:ethylene-2,2'-bis(dithio)bis(ethanol)