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.
Tanouchi
Y
Y
Eye Research Institute of Oakland University, Rochester, Michigan 48063.
Shichi
H
H
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D002412:Cations / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D007376:Interleukin-2 / Q000096:biosynthesis; D007930:Leucine / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000517:prevention & control*; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism; D014605:Uveitis / Q000517:prevention & control*
D002412:Cations; D007376:Interleukin-2; D011714:Pyrans; C003417:tetranactin; D007930:Leucine; D013936:Thymidine; D014529:Uridine