Immunosuppressive and anti-proliferative effects of a macrotetrolide antibiotic, tetranactin.

The macrotetrolide tetranactin suppressed the appearance of experimental autoimmune uveoretinitis induced in Lewis rats with a soluble retinal antigen (S-antigen). The drug at 1 ng/ml inhibited the mitogen activation of unfractionated lymphocytes; incorporation of radiolabelled precursors such as thymidine, uridine and leucine into the cells was markedly reduced. The synthesis and release of IL-2 by mitogen-activated lymphocytes was significantly suppressed in the presence of tetranactin. Incorporation of 45Ca was also inhibited, while intracellular Na+ levels were increased. In view of the ionophore property of tetranactin, it was suggested that the drug might demonstrate its immunosuppressive effect by affecting intracellular cation concentrations.