A NEW ANTIRHEUMATIC DRUG, T-614, EFFECTIVELY SUPPRESSES THE DEVELOPMENT OF AUTOIMMUNE ENCEPHALOMYELITIS

In the present study, we examined the therapeutic effects of T-614 hyl sulfonylamino-6-phenoxy-4H-1-benzopyran-4-one), a new anti-rheumatic d rug, on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). T-614 dose-dependently suppressed the develop ment of active EAE induced in Lewis rats by immunization with myelin b asic protein (MBP) when administered for 2 weeks starting on the day o f immunization (day 0 to 14). Amelioration of clinical signs was also obtained by the treatment at the effector phase (day 7 to 14) of the d isease. Furthermore, T-614 treatment of recipient rats that had receiv ed MBP-sensitized lymphoid cells resulted in suppression of the clinic al severity of EAE. Immunohistological examination revealed that the n umber of TCR alpha beta-expressing T cells and the extent of MHC class II expression in the spinal cord of rats treated with T-614 was marke dly reduced. In vitro study using MBP-specifIc T cells showed that the addition of T-614 inhibited the proliferative responses of T cells an d the production of pro-inflammatory cytokines such as IFN-gamma, IL-6 and TNF produced by T and accessory cells. Taken together, these find ings imply that T-614 suppresses the development of EAE by inhibiting the proliferation of autoreactive T cells and pro-inflammatory cytokin e production not only by T cells but also by macrophages/microglia. Th is may be attributable to the result that T-614 is more effective at t he effector phase rather than the induction phase. Thus, this drug has a potential value for the treatment of various T cell-mediated autoim mune diseases including multiple sclerosis (MS) as well as rheumatoid arthritis. (C) 1998 Elsevier Science B.V. All rights reserved.