[Effects of novel immunosuppressant FK 506 in acute experimental allergic encephalomyelitis].
Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease. It is widely used as an animal model of multiple sclerosis (MS). We studied the prophylactic effects of FK 506 electrophysiologically and immunohistochemically in acute EAE. Female Lewis rats were sensitized with guinea pig spinal cord in complete Freund's adjuvant. FK 506 suspended in distilled water was orally administered at 1.0, 3.2, 5.0 or 10.0 mg/kg per day for 12 successive days starting from the day of sensitization. A placebo was used as the control. Administration of FK 506 at doses of 3.2 mg/kg per day and over significantly delayed the onset of clinical signs. However, the FK 506 group showed a relapse or a chronic state following the onset of EAE. We made a time course recording of cortical somatosensory evoked potential (cortical SEP: P 15). P 15 latency in the placebo group was significantly delayed in accordance with the clinical signs and showed immediate improvement upon recovery. Prolongation of P 15 latency in the FK 506 group also occurred concomitantly with the clinical signs, but the delay continued after the loss of symptoms as well. After the onset of EAE, the infiltrating lymphocyte subset was examined by the avidin-biotin peroxidase complex (ABC) method in the lumbar spinal cord. In the placebo group, the number of OX3+ (Ia) cells and the W 3 25+: OX8+ (helper/inducer T: suppressor/cytotoxic T) ratio clearly reflected the development and remission of EAE. In the FK 506 group, however, increases in OX8+ lymphocytes were observed irrespective of clinical sign fluctuation, and there were corresponding decreases in the W 3/25+: OX8+ ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, Kagawa Medical School, Japan.
K
K
Deguchi
H
H
Takeuchi
H
H
Miki
A
A
Yamada
T
T
Touge
S
S
Terada
M
M
Nishioka
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D016559:Tacrolimus