Immunosuppression by gramicidin S of experimental autoimmune uveoretinitis, pinealitis and autoimmune encephalomyelitis.
Using an in vitro lymphocyte proliferation assay we screened several cyclic peptide antibiotics (bacitracin, oleandomycin, capreomycin, colistin, virginiamycin, and gramicidin S) for their immunosuppressive activity. Gramicidin S (GrS) was found to inhibit [3H]-thymidine incorporation into concanavalin A-stimulated and E coli lipopolysaccharide-stimulated lymphocytes. In vivo studies, experimental autoimmune uveoretinitis (EAU) and pinealitis were induced in female Lewis rats by immunization with bovine S-antigen and experimental autoimmune encephalomyelitis (EAE) were induced by immunization of rats with rat brain homogenates. GrS suppressed the onset of these inflammatory diseases at nontoxic concentrations. Evidence was obtained that GrS inhibits [3H]-thymidine incorporation into lymphocytes by preventing transport of the compound across the membrane. Since GrS binds to various cell membranes, GrS would suppress the proliferation of not only lymphocytes but also of other immune cells by modifying cell membrane properties. The present study indicates that a search for compounds which cause proper cell membrane modification should be a worthwhile strategy for development of immunosuppressive drugs.
Matsushima
S
S
Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI.
Yoshitoshi
T
T
Shichi
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D019393:Arrestin; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000473:pathology; D003208:Concanavalin A / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005136:Eye Proteins / Q000008:administration & dosage; D005260:Female; D006096:Gramicidin / Q000494:pharmacology* / Q000627:therapeutic use; D007114:Immunization; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010870:Pineal Gland / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy* / Q000473:pathology; D013116:Spinal Cord / Q000201:enzymology; D013154:Spleen / Q000166:cytology; D013936:Thymidine / Q000378:metabolism; D015866:Uveitis, Posterior / Q000188:drug therapy / Q000473:pathology
D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D003208:Concanavalin A; D006096:Gramicidin; D010744:Phosphoric Monoester Hydrolases; C022627:sedoheptulose-bisphosphatase; D013936:Thymidine