Immunosuppressive effect of FK506 on experimental allergic encephalomyelitis in rats.
We investigated the effect of a new immunosuppressant, FK506, on the development of experimental allergic encephalomyelitis (EAE) in rats. EAE developed in 100% of rats immunized with myelin basic protein (MBP) in complete Freund's adjuvant. FK506 in doses of 1.0 mg/kg/day or more prevented the clinical signs of EAE for at least 50 days, when administered intramuscularly 5 days a week for 2 weeks starting on the day of immunization (days 0-4 and days 7-11), and a similar result was obtained, when the compound was given for 5 days (days 0-4). FK506, however, showed a significant but weak effectiveness when started from 7 days after immunization. Delayed-type hypersensitivity (DTH) to MBP developed before EAE, and anti-MBP antibody levels increased. Both humoral and cellular immune response to MBP were completely suppressed in rats treated with FK506. From these results, it is presumed that immunosuppression of cell-mediated immunity and/or humoral immunity by the treatment of FK506 actually causes the decreased incidence noted in the experiment for the development of EAE.
Inamura
N
N
Exploratory Research Laboratory, Fujisawa Pharmaceutical Co., Ltd, Ibaraki, Japan.
Hashimoto
M
M
Nakahara
K
K
Nakajima
Y
Y
Nishio
M
M
Aoki
H
H
Yamaguchi
I
I
Kohsaka
M
M
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus; D013997:Time Factors
D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D011725:Pyridines; D016559:Tacrolimus