A new anti-rheumatic drug, T-614, effectively suppresses the development of autoimmune encephalomyelitis.

Abstract

In the present study, we examined the therapeutic effects of T-614 (3-formylamino-7-methylsulfonylaminoxy-4H-1-benzopyran-4-one), a new anti-rheumatic drug, on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). T-614 dose-dependently suppressed the development of active EAE induced in Lewis rats by immunization with myelin basic protein (MBP) when administered for 2 weeks starting on the day of 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 disease. Furthermore, T-614 treatment of recipient rats that had received MBP-sensitized lymphoid cells resulted in suppression of the clinical severity of EAE. Immunohistological examination revealed that the number 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 markedly reduced. In vitro study using MBP-specific T cells showed that the addition of T-614 inhibited the proliferative responses of T cells and the production of pro-inflammatory cytokines such as IFN-gamma, IL-6 and TNF produced by T and accessory cells. Taken together, these findings imply that T-614 suppresses the development of EAE by inhibiting the proliferation of autoreactive T cells and pro-inflammatory cytokine production not only by T cells but also by macrophages/microglia. This may be attributable to the result that T-614 is more effective at the effector phase rather than the induction phase. Thus, this drug has a potential value for the treatment of various T cell-mediated autoimmune diseases including multiple sclerosis (MS) as well as rheumatoid arthritis.

• Authors: Y Aikawa, N Tanuma, T Shin, S Makino, K Tanaka, Y Matsumoto
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 89 Issue 1-2 Pg. 35-42 (Aug 14 1998) ISSN: 0165-5728 [Print] Netherlands
• PMID: 9726823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antirheumatic Agents
• Benzopyrans
• Interleukin-1
• Interleukin-6
• Myelin Basic Protein
• Sulfonamides
• Tumor Necrosis Factor-alpha
• T 614
• Interferon-gamma

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (immunology, pharmacology)
• Antirheumatic Agents (immunology, pharmacology)
• Arthritis, Rheumatoid (drug therapy)
• Benzopyrans (immunology, pharmacology)
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, immunology, pathology)
• Interferon-gamma (analysis)
• Interleukin-1 (biosynthesis, immunology)
• Interleukin-6 (biosynthesis, immunology)
• Macrophages (drug effects, immunology, metabolism)
• Microglia (drug effects, immunology, metabolism)
• Myelin Basic Protein (immunology, pharmacology)
• Rats
• Rats, Inbred Lew
• Spinal Cord (immunology, pathology)
• Sulfonamides (immunology, pharmacology)
• T-Lymphocytes (drug effects, immunology, metabolism)
• Tumor Necrosis Factor-alpha (analysis)