FK506 and rapamycin: differential sensitivity of human, baboon, cynomolgus monkey, dog and pig lymphocytes.
It has recently been suggested that there are species differences in the sensitivity of T lymphocytes to the immunosuppressive effect of FK506. We explore this phenomenon further and compare FK506 with rapamycin in lymphocytes from dog, pig, baboon, cynomolgus monkey and man. We found that the relative sensitivity of T cells to FK506 did not necessarily correlate with their sensitivity to rapamycin, further emphasising the different mode of action of each drug. The serum may alter results of dose-response curves, and thus autologous serum may introduce an uncontrolled variable when different species are being compared in vitro. We conclude that the differences in sensitivity of lymphocytes from various species to FK506 and rapamycin are independent of each other, and these differences are likely to reflect variation in the overall interactive pathways involved in T-cell mitogenesis.
Metcalfe
S
S
Department of Surgery, Addenbrookes Hospital, Cambridge, United Kingdom.
Svvennsen
R
R
Calne
R Y
RY
D000818:Animals; D004285:Dogs; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008252:Macaca fascicularis; D010215:Papio; D020123:Sirolimus / Q000494:pharmacology*; D013045:Species Specificity; D013552:Swine; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus