SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis. III. Immunosuppressive efficacy.
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 0.5 microM and 0.2 microM, 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.
Kurosawa
Kazuhiko
K
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan. kurosawa9630@nifty.com
Takahashi
Kosaku
K
Fujise
Nobuaki
N
Yamashita
Yasushi
Y
Washida
Naohiro
N
Tsuda
Eisuke
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009574:Nitro Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011753:Pyrones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D016038:Skin Transplantation / Q000276:immunology*
D007166:Immunosuppressive Agents; D009574:Nitro Compounds; D011753:Pyrones; C435067:SNF 4435C; C435066:SNF 4435D