The modulatory effects of IL-1β and TNFα on the rat paw edema induced by B 1 agonists have been analyzed. In naive rats, ID injection of B 1 agonists, des-Arg 9 -bradykinin and des-Arg 1 0 -kallidin (up to 300 nmol), causes a minimal increase in paw volume, while the B 2 agonist tyrosine 8 -bradykinin (0.3-10 nmol) induces graded paw edema. The injection of des-Arg 9 -bradykinin (10-100) nmol or des-Arg 1 0 -kallidin (1-100 nmol), in paws pre-treated with IL-1β or TNFα (both 5 ng/paw; 60 and 30 min prior, respectively), caused a graded edema formation. The edemas induced by des-Arg 9 -bradykinin (100 nmol) were evident at 15 min, reaching the maximum 60 and 30 min after treatment with IL-1β (0.64 +/- 0.06 ml) or TNFα (0.47 +/- 0.05 ml), respectively, being reduced at 360 min. The B 1 antagonist des-Arg 9 -NPC 17731 (1-30 nmol), but not the B 2 antagonist Hoe 140 (10 nmol), produced marked inhibition of des-Arg 9 -bradykinin-induced paw edema. Dexamethasone (0.5 mg/kg, SC, 4 h) or cycloheximide (1.5 mg/kg, SC, 6 h) significantly prevented the edema caused by des-Arg 9 -bradykinin (100 nmol) in rats treated with IL-1β (81 +/- 5% and 59 +/- 3%) or TNFα (78 +/- 4% and 43 +/- 2%). Indomethacin (2 mg/kg, IP) or meloxicam (3 mg/kg, IP), 1 h prior, significantly reduced the edema induced by des-Arg 9 -bradykinin (100 nmol) in IL-1β (40 +/- 6% and 69 +/- 8%) or TNFα (43 +/- 3% and 53 +/- 9%) treated rats. It is suggested that ID injection of the IL-1β or TNFα, produced up-regulation of B 1 receptor-mediated paw edema, being this effect sensitive to dexamethasone and cycloheximide and to cyclo-oxygenase pathway.