Suppression of in vitro cellular immune response by nitrogen-containing terpene alcohol derivatives.
A series of nitrogen-containing terpene alcohol derivatives were tested for their immunosuppressive effects in vitro, and KYKC-407 (erythro-1-(1-imidazolyl)-3,7,11-trimethyl-dodecane-2(S),3(R)-diol) was found to be the most effective in suppressing the induction of cytotoxic T cell (CTL) activity. CTL induction in the coculture of C3H spleen cells with mitomycin C-treated BALB/c spleen cells was suppressed by more than 90% when 4 microM KYKC-407 was added to the culture. Under these conditions, lymphocyte proliferation was also suppressed to a similar extent by this compound. Flow cytometric analysis revealed that KYKC-407 strongly inhibited the proliferation of CD8+ T cell subset, but showed less suppressive effects on CD4+ T cells. In contrast to cyclosporin A, KYKC-407 at 1-4 microM did not inhibit the proliferative response to concanavalin A. Further, KYKC-407 suppressed CTL induction even in the presence of exogenous IL-2, thus suggesting that the compound does not exert its effects through inhibiting IL-2 production.
Okada
Y
Y
Department of Biotechnology, Faculty of Engineering, Okayama University, Japan.
Matono
N
N
Shiono
M
M
Takai
T
T
Hikida
M
M
Ohmori
H
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*
D007093:Imidazoles; D007166:Immunosuppressive Agents; D007376:Interleukin-2; C104412:KYKC 407; D013729:Terpenes