Immunosuppressive effects of polynactins (tetranactin, trinactin and dinactin) on experimental autoimmune uveoretinitis in rats.
Macrotetrolide antibiotic polynactins [dinactin, trinactin and tetranactin (1:4:5)] are hydrophobic cyclic esters produced by Streptomyces aureus. Polynactins (PN) and their major component tetranactin (TN) delayed or suppressed the onset of S-antigen-induced experimental autoimmune uveoretinitis (EAU) in Lewis rats. Termination of treatment with PN or TN before day 14 of immunization resulted in a delayed onset of EAU in many animals. Thus, the immunosuppressive effect of PN and TN was not lasting. PN and TN suppressed anti-S-antigen antibody formation. Skin hypersensitivity tests indicated suppression by PN of the delayed-type rather than Arthus type hypersensitivity to S-antigen. PN, TN and trinactin all inhibited 3H-thymidine incorporation into concanavalin A-treated lymphocytes at the early stage of cell activation. For each drug, 50% inhibition was obtained at about 0.1 ng/ml. Under the incubation condition that the cells were exposed to TN for 21 hours, cell viability remained unchanged up to 100 ng/ml of TN. It is evident that PN and TN suppress T-lymphocyte proliferation without cell injury. These results suggest that PN and TN inhibit the onset of EAU primarily through the suppression of cell-mediated immunity but also by affecting humoral immunity.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000941:Antigens; D019393:Arrestin; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy*; D002478:Cells, Cultured; D005136:Eye Proteins; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D018942:Macrolides; D011714:Pyrans / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000188:drug therapy*; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D018942:Macrolides; D011714:Pyrans; C003417:tetranactin; C009584:trinactin; C016520:dinactin