Reduction of disease causative T-cells in experimental autoimmune disease models by a new antirheumatic drug, TAK-603.
We investigated the mode of action of a new quinoline derivative, TAK-603 (ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl) quinoline-3-carboxylate), in adjuvant arthritis (AA), a model of rheumatoid arthritis. AA rat splenocytes transferred the arthritis to normal syngeneic rats upon inoculation, but the cells from AA rats treated with TAK-603 (6.25 mg/kg/day) caused only mild arthritis with significantly less foot pad swelling and a lower arthritis score. An effect of TAK-603 in the induction phase of AA was suggested. TAK-603 had little effect on CD4+ and CD8+ T-cell populations in the AA rat splenocytes. We therefore estimated the frequency of T-cells which are reactive to the so-called disease causative antigen using a limiting dilution assay (LDA). The ratio of T-cells responsive to PPD, which increased in AA rat splenocytes with the severity of the arthritis, was reduced in AA rats treated with TAK-603. Furthermore, the ratio of MBP (myelin basic protein)-reactive T-cells, which were generated in experimental allergic encephalomyelitis (EAE) rats, were also reduced by TAK-603 administration. These data suggest that TAK-603 acts on the immune system and reduces the number of cells reactive to the relevant antigen.
Ohta
Y
Y
Pharmaceutical Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Fukuda
S
S
Makino
H
H
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D016516:CD4-CD8 Ratio; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D016131:Lymphocyte Subsets; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D014230:Triazoles / Q000494:pharmacology*
D018501:Antirheumatic Agents; D011804:Quinolines; D014230:Triazoles; C104411:TAK 603