抄録
Inhibition of the development of adjuvant arthritis (AA) in male LEW rats by a daily, oral dose of 0.3 mg/kg of methotrexate (MTX) was examined in terms of timing and duration of treatment. A complete suppression of AA development until day 21 was obtained by dosing from days 5 to 14 after CFA inoculation in the hind foot, as well as that from day 0 to day 18 throughout, while AA symptoms appeared in a dose-related manner as the daily doses decreased to 0.1 and 0.05 mg/kg. The same schedule of treatment also inhibited completely the onset of CP 20961-induced, AA-like polyarthritis in male LEW rats. The autopsy findings on the rats being free from AA development were nearly close to those from normal controls. However, their draining lymph nodes were found to be still much larger on day 21, and AA, even to a mild degree, developed late with a maximum on day 28. Dosing from days 5-9 delayed significantly AA onset for a few days followed by a rapid development of the disease, and in addition, decreased DTH responsiveness in skin and IL -2 production in cultured lymph node cells, both of which were determined by PPD stimulation on day 11. MTX had no effect on the time courses of both the primary and secondary swelling in the hind feet. From these results, it is concluded that MTX may act to delay onset time of AA, mainly by suppressing the progression of T-cell maturation and activation beginning from day 4 or 5, and secondarily by preventing any cross-talk between T-cells and macrophages, which occurs around day 10.
