Chen M F, Suzuki H, Maruyama M, Yano S
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Immunol Lett. 1991 Aug;29(3):255-9. doi: 10.1016/0165-2478(91)90179-e.
Although FK-506 has been widely investigated as a potent suppressor of organ allograft rejection in animals, little is known about the effect of FK-506 on normal animals. In this study, we investigated the influence of FK-506 on the thymus and spleen in normal C3H/He mice at the age of 5 weeks. Mice were given dosages of FK-506 varying between 0.3 and 30 mg/kg/day intramuscularly for 5 days. After treatment with FK-506, the total number of lymphocytes in the thymus was significantly decreased in a dose-dependent manner; however, no change was evident in the total number of lymphocytes in the spleen. FK-506 also influenced the immunophenotypes in thymocytes, but not in splenocytes. The absolute number of CD4+ CD8- or CD4- CD8+ thymocytes decreased significantly in the 0.3 mg/kg/day-treated group. CD4+ CD8-, but not CD4-CD8+ thymocytes decreased further in the 1 mg/kg/day-treated group. Neither subpopulation decreased any further with continuing administration. On the other hand, the number of CD4+ CD8+ thymocytes did not decrease significantly in the 0.3 mg/kg/day-treated group, whereas it did decrease significantly in the 1 mg/kg/day-treated group, decreased further with the increase in dosage of FK-506, and decreased markedly in the 30 mg/kg/day group, The number of CD4-CD8-thymocytes did not show any change, even in the high-dosage groups. These results indicate that FK-506 influences the subpopulations of thymocytes according to its dosage. At a lower dosage, it affects mature CD4+ CD8- or CD4- CD8+ cells, but not immature CD4+ CD8+ and CD4-CD8- cells.2
