Biological activities of IC201 ((3S,8E)-1,3-dihydroxy-8-decen-5-one), a low molecular weight immunomodulator produced by Streptomyces.
IC201 was found in cultured broth of Streptomyces cirratus as an antitumor antibiotic which was effective in retarding growth of the established solid tumor of Ehrlich carcinoma by treatment starting 8 days after tumor inoculation. It retarded growth of the established solid tumor of IMC carcinoma but had no cytotoxicity at 100 micrograms/ml. IC201 treatment kept NK cell activity of tumor-bearing mice at normal level and stimulated cytostatic activity of peritoneal macrophages. It stimulated phagocytosis of yeast and phorbol myristate acetate-elicited superoxide production by peritoneal macrophages. The addition of IC201 to P388D1 cell cultures enhanced release of interleukin 1 (IL-1) into cultured supernatant but it affected lipopolysaccharide-induced IL-1 production. Although the addition to macrophage-depleted cultures did not show any stimulatory effect, mixed lymphocyte culture reaction was augmented in cultures using spleen cells as stimulator cells taken from mice given IC201. Results indicate that IC201 primarily activates macrophages and the activation may cause modulation of immune responses.
Mizutani
S
S
Institute for Chemotherapy, Shizuoka, Japan.
Odai
H
H
Masuda
T
T
Iijima
M
M
Osono
M
M
Hamada
M
M
Naganawa
H
H
Ishizuka
M
M
Takeuchi
T
T
D000276:Adjuvants, Immunologic / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002460:Cell Line; D002478:Cells, Cultured; D005233:Fatty Alcohols / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005285:Fermentation; D007375:Interleukin-1 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010587:Phagocytosis / Q000187:drug effects; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D005233:Fatty Alcohols; D007375:Interleukin-1; C060113:1,3-dihydroxy-8-decen-5-one