M. Hisadome et al., 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, International journal of immunopharmacology, 18(6-7), 1996, pp. 379-384
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