実験的アレルギー性脳脊髄炎（EAE）における免疫抑制剤FK 506の効果

EFFECTS OF NOVEL IMMUNOSUPPRESSANT FK 506 IN ACUTE EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

　実験的アレルギー性脳脊髄炎（EAE）は細胞性免疫を介する病態で，多発性硬化症のモデルである。今回，新しい免疫抑制剤FK 506のEAE抑制効果を電気生理学的，免疫組織化学的に検討した。雌Le—wisラットをモルモットの脊髄homogenateと完全Freund's adjuvantのemulsionで感作し，感作当日から11日目までFK 506（1.0，3.2，5.0，10.0mg／kg）を連日経口的に投与した。対照としてPlaceboを同様に投与した。FK 506 3.2mg／kg以上の投与によりEAEの発症は有意に遅延したが，EAE発症後は再燃，慢性化を認めた。経時的な皮質体性感覚誘発電位（cortical SEP：P15）の記録ではP15の潜1暗はFK 506，placebo両群ともに症状の消長とよく一致していたが，FK 506群では症状消失後も潜時の延長が見られた。EAE発症後，腰髄に浸潤したリンパ球サブセットの検索では，FK 506群で症状の変動に関係なくOX 8^＋（suppressor／cytotoxic T）細胞の増加が見られた。FK 506は強力なEAE抑制作用を持つが，短期間の投与はその期間終了後，生体内免疫調節機構に影響を与え，逆にEAEの増悪をまねく可能性が示唆された。

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease. It is wi-dely used as an animal model of multiple sclerosis (MS). We studied the prophylactic effects of FK 506 electrophysiologically and immunohistochemi-cally in acute EAE. Female Lewis rats were sen-sitized 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 delay-ed the onset of clinical signs. However, the FK 506 group showed a relapse or a chronic state fol-lowing the onset of EAE. We made a time course recording of cortical somatosensory evoked poten-tial (cortical SEP : P 15). P15 latency in the pla-cebo group was significantly delayed in accordance with the clinical signs and showed immediate im-provement upon recovery. Prolongation of P 15 latency in the FK 506 group also occurred conco-mitantly with the clinical signs, but the delay cont-inued after the loss of symptoms as well. After the onset of EAE, the infiltrating lymphocyte sub-set 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 W3/25⁺ : 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 fluctua-tion, and there were corresponding decreases in the W 3/25⁺ : OX8⁺ ratio. These results indicate that FK 506 effectively suppresses the onset of EAE, whereas an end of administration may aggravate EAE by an affected immune regulating mechanism.