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.