Enhancement of in vivo production of IL-1 alpha and IL-6 in mice by Y-25510, a 1H-pyrazolo[3,4-b]pyridine-1 acetic acid derivative.

The serum concentrations of interleukin(IL)-1 alpha and IL-6 in C57BL/6 and C3H/HeN mice reached the maximum at 12-16 h after the intravenous treatment with (+/-)-3-[4-(2-dimethylamino-1-methylethoxy)- phenyl]-1H-pyrazolo[3,4-b]pyridine-1-acetic acid (Y-25510) at a dose of 3 mg/kg, and the concentration of IL-10 did at 20 h after the treatment. By repeated treatments with Y-25510 to C57BL/6 mice for 14 days, the maximal values of IL-1 alpha and IL-6 at day 14 were respectively 6.6 times and 5.7 times relative to those on day 1. Neither the counts of peripheral leukocytes nor those of platelets were, however, increased until day 15. The repeated treatment with Y-25510 followed by anti-IL-10 antibody for 14 days was significantly more effective than that with Y-25510 alone in increasing the concentrations of IL-1 alpha and IL-6 in C3H/HeN mice. In addition, both the counts of peripheral leukocytes and platelets were significantly increased at day 18. In conclusion, Y-25510 enhanced not only the production of endogenous IL-1 alpha and IL-6 but also that of IL-10 in healthy mice. As a result, in normal conditions, both the counts of peripheral leukocytes and platelets were never increased because of the inhibitory effect of endogenously produced IL-10.