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 intravenou s treatment with ethoxy)phenyl]-1H-pyrazolo[3,4-b]pyridine-1-acetic ac id (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 C5 7BL/6 mice for 14 days, the maximal values of IL-1 alpha and IL-6 at d ay 14 were respectively 6.6 times and 5.7 times relative to those on d ay 1. Neither the counts of peripheral leukocytes nor those of platele ts 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 concentr ations of IL-1 alpha and IL-6 in C3H/HeN mice. In addition, both the c ounts of peripheral leukocytes and platelets were significantly increa sed 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 m ice. As a result, in normal conditions, both the counts of peripheral leukocytes and platelets were never increased because of the inhibitor y effect of endogenously produced IL-10. Copyright (C) 1996 Internatio nal Society for Immunopharmacology