MODULATION OF KININ B-1 BUT NOT B-2 RECEPTORS-MEDIATED RAT PAW EDEMA BY IL-1-BETA AND TNF-ALPHA

The modulatory effects of IL-1 beta and TNF alpha on the rat paw edema induced by B-1 agonists have been analyzed. In naive rats, ID injecti on of B-1 agonists, des-Arg(9)-bradykinin and des-Arg(10)-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(10)-k allidin (1-100 nmol), in paws pre-treated with IL-1 beta or TNF alpha (both 5 ng/paw; 60 and 30 min prior, respectively), caused a graded ed ema formation. The edemas induced by des-Arg(9)-bradykinin (100 nmol) were evident at 15 min, reaching the maximum 60 and 30 min after treat ment with IL-1 beta (0.64 +/- 0.06 ml) or TNF alpha (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-1 beta (81 +/- 5% and 59 +/- 3%) o r TNF alpha (78 +/- 4% and 43 +/- 2%). Indomethacin (2 mg/kg, IP) or m eloxicam (3 mg/kg, IP), 1 h prior, significantly reduced the edema ind uced by des-Arg(9)-bradykinin (100 nmol) in IL-1 beta (40 +/- 6% and 6 9 +/- 8%) or TNF alpha (43 +/- 3% and 53 +/- 9%) treated rats. It is s uggested that LD injection of the IL-1 beta or TNF alpha, produced up- regulation of B-1 receptor-mediated paw edema, being this effect sensi tive to dexamethasone and cycloheximide and to cyclo-oxygenase pathway . (C) 1998 Elsevier Science Inc.