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 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.
Coppi
G
G
Research Centre, Poli Industria Chimica S.p.A., Milan, Italy.
Manzardo
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D006087:Graft vs Host Reaction / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000276:immunology; D009929:Organ Size / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D004137:Dinitrochlorobenzene; D013844:Thiazoles; D053778:Thiazolidines; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid