EXPERIMENTAL IMMUNOLOGICAL SCREENING-TESTS ON PIDOTIMOD

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]- thiazolidine-4- carboxylic acid, PGT/1A, CAS 121808-62-6), a new biological response m odifier, was administered to immunodepressed (by prednisolone, cycloph osphamide or methotrexate) mice by oval and intraperitoneal route (res pectively up to 400 and 200 mg/kg) during several days (up to 9 days). The stimulatory action of the drug on cell-mediated immunity is inves tigated by measuring the rosette formation by the murine splenic lymph ocytes ex vivo, by T- and B-lymphocytes ex vivo proliferative response to mitogens, by dinitrochlorobenzene delayed hypersensitivity induced on the ear, by the graft-versus-host reaction with immunodepressed mi ce as donors. In all tests pidotimod reveals a potent action in restor ing the depressed reactivity. The action of pidotimod on humoral immun ity is showed in two tests where the antibody response is induced by a thymus dependent (sheep erythrocytes) or a thymus independent (lipopo lysaccharide) antigen. Pidotimod was active in both rests. Macrophage functions, anion superoxide production and the non-stimulated ex vivo chemotaxis reveal that pidotimod significantly reduces the immunodepre ssant action of prednisolone; particularly in i.p. treated mice the ch emotaxis is likely to be restored to the levels of the non-immunodepre ssed controls. The colloidal china ink blood clearance in vivo in immu nodepressed mice, after pidotimod treatment, results similar to that f ound in the control mice.