Abstract
The effects of Ca-antagonists on the release of IL-1β by LPS stimulated human blood monocytes (HBMs) were examined by radioimmunoassay. Caantagonists used were nicardipine, nifedipine, nimodipine, flunarizine, verapamil and diltiazem. Flunarizine strongly inhibited the IL-1β release from HBMs by LPS with an IC50 of 25.9 μM. Diltiazem and verapamile inhibited at the higher concentration (IC50> 160 μM), but the other Ca-antagonists, dihydropyridine type, such as nicardipine, nifedipine and nimodipine did not affect the IL-1β release from HBMs. In order to investigate the mechanism of IL-1β inhibition of flunarizine, forskolin was used. Forskolin was 2 fold potentiated the IL-1β release from HBMs stimulated by LPS. Flunarizine pretreatment with dose of IC50 completely inhibited IL-1β release from HBMs increased by forskolin.
Taken together, these results suggest that the mechanism of the inhibition of IL-1β release from HBMs by flunarizine may be closely related to cyclic AMP.
