SNF4435C and D, Novel Immunosuppressants Produced by a Strain of Streptomyces spectabilis: III. Immunosuppressive Efficacy

• Published in: Journal of antibiotics 2002/01/25, Vol.55(1), pp.71-77
• Main Authors: KUROSAWA, KAZUHIKO, TAKAHASHI, KOSAKU, FUJISE, NOBUAKI, YAMASHITA, YASUSHI, WASHIDA, NAOHIRO, TSUDA, EISUKE
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Graft Survival - drug effects; Humans; Hypersensitivity, Delayed - immunology; Hypersensitivity, Delayed - prevention & control; Immunomodulators; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; Lymphocyte Culture Test, Mixed; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nitro Compounds - administration & dosage; Nitro Compounds - pharmacology; Pharmacology. Drug treatments; Pyrones - administration & dosage; Pyrones - pharmacology; Rats; Rats, Inbred F344; Skin Transplantation - immunology
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.55.71

Novel immunosuppressants, SNF4435C and D produced by a strain of Streptomyces spectabilis, were examined for their pharmacodynamical profiles. SNF4435C and D suppressed the responses of both murine splenocytes and human peripheral blood lymphocytes in the mixed lymphocyte reaction (MLR) with IC50 values of 0.5μM and 0.2μM, respectively. In the mouse MLR experiments, SNF4435C and D did not block the production of interleukin-2 (IL-2) and the compounds-induced suppression was not restored by the addition of exogeneous IL-2. In addition, the significant inhibitory action was still retained even when SNF4435C or D was added after 48 hours from the start of the culture. These results were distinct from the behaviors observed with FK-506. SNF4435C, the major component, suppressed mouse delayed type hypersensitivity (DTH) and prolonged rat skin allograft survival.