Experimental immunological screening tests on pidotimod.

Abstract

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new biological response modifier, was administered to immunodepressed (by prednisolone, cyclophosphamide or methotrexate) mice by oral and intraperitoneal route (respectively 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 investigated by measuring the rosette formation by the murine splenic lymphocytes 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 mice as donors. In all tests pidotimod reveals a potent action in restoring the depressed reactivity. The action of pidotimod on humoral immunity is showed in two tests where the antibody response is induced by a thymus dependent (sheep erythrocytes) or a thymus independent (lipopolysaccharide) antigen. Pidotimod was active in both tests. Macrophage functions, anion superoxide production and the non-stimulated ex vivo chemotaxis reveal that pidotimod significantly reduces the immunodepressant action of prednisolone; particularly in i.p. treated mice the chemotaxis is likely to be restored to the levels of the non-immunodepressed controls. The colloidal china ink blood clearance in vivo in immunodepressed mice, after pidotimod treatment, results similar to that found in the control mice.