FK506 potentiates steroid-induced T-cell apoptosis.
BACKGROUND
FK506 and glucocorticoids are used for allograft rejection, graft-versus-host disease, and autoimmune diseases.


METHODS
We investigated the combined effect of FK506 and glucocorticoids on T-cell apoptosis.


RESULTS
Dexamethasone injection in mice reduced the number of CD4+CD8+ thymocytes by increasing DNA fragmentation. Pretreatment with FK506 significantly augmented thymocyte DNA fragmentation induced by dexamethasone injection. Increased thymic apoptosis resulted in the disappearance of CD4+CD8+ thymocytes after FK506/dexamethasone injection. In addition to thymocytes, mature human peripheral blood T cells undergo apoptosis by exposure to dexamethasone in vitro. FK506 synergistically enhanced dexamethasone-mediated apoptosis of human peripheral blood T cells.


CONCLUSIONS
Thus, our results showed that FK506 enhanced dexamethasone-induced apoptosis of T cells in vivo and in vitro. This interaction may enhance the therapeutic immunosuppression achieved by these two drugs.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan. e.g.uchi@net.nagasaki-u.ac.jp
Eguchi
K
K
Kawabe
Y
Y
Origuchi
T
T
Tominaga
M
M
Nagataki
S
S
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016559:Tacrolimus