Campos M M, Souza G E, Calixto J B
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Peptides. 1998;19(7):1269-76. doi: 10.1016/s0196-9781(98)00087-4.
The modulatory effects of IL-1beta and TNF alpha on the rat paw edema induced by B1 agonists have been analyzed. In naive rats, i.d. injection of B1 agonists, des-Arg9-bradykinin and des-Arg10-kallidin (up to 300 nmol), causes a minimal increase in paw volume, while the B2 agonist tyrosine8-bradykinin (0.3-10 nmol) induces graded paw edema. The injection of des-Arg9-bradykinin (10-100) nmol or des-Arg10-kallidin (1-100 nmol), in paws pre-treated with IL-1beta or TNF alpha (both 5 ng/paw; 60 and 30 min prior, respectively), caused a graded edema formation. The edemas induced by des-Arg9-bradykinin (100 nmol) were evident at 15 min, reaching the maximum 60 and 30 min after treatment with IL-1beta (0.64 +/- 0.06 ml) or TNF alpha (0.47 +/- 0.05 ml), respectively, being reduced at 360 min. The B1 antagonist des-Arg9-NPC 17731 (1-30 nmol), but not the B2 antagonist Hoe 140 (10 nmol), produced marked inhibition of des-Arg9-bradykinin-induced paw edema. Dexamethasone (0.5 mg/kg, s.c., 4 h) or cycloheximide (1.5 mg/kg, s.c., 6 h) significantly prevented the edema caused by des-Arg9-bradykinin (100 nmol) in rats treated with IL-1beta (81 +/- 5% and 59 +/- 3%) or TNF alpha (78 +/- 4% and 43 +/- 2%). Indomethacin (2 mg/kg, i.p.) or meloxicam (3 mg/kg, i.p.), 1 h prior, significantly reduced the edema induced by des-Arg9-bradykinin (100 nmol) in IL-1beta (40 +/- 6% and 69 +/- 8%) or TNF alpha (43 +/- 3% and 53 +/- 9%) treated rats. It is suggested that i.d. injection of the IL-1beta or TNF alpha, produced up-regulation of B1 receptor-mediated paw edema, being this effect sensitive to dexamethasone and cycloheximide and to cyclo-oxygenase pathway.
已分析了白细胞介素 - 1β（IL - 1β）和肿瘤坏死因子α（TNFα）对B1激动剂诱导的大鼠爪部水肿的调节作用。在未处理的大鼠中，皮内注射B1激动剂去 - 精氨酸9 - 缓激肽和去 - 精氨酸10 - 胰激肽（高达300 nmol），爪部体积仅有轻微增加，而B2激动剂酪氨酸8 - 缓激肽（0.3 - 10 nmol）则诱导出分级的爪部水肿。在预先用IL - 1β或TNFα处理的爪部（均为5 ng/爪，分别提前60分钟和30分钟）注射去 - 精氨酸9 - 缓激肽（10 - 100）nmol或去 - 精氨酸10 - 胰激肽（1 - 100 nmol），会导致分级的水肿形成。去 - 精氨酸9 - 缓激肽（100 nmol）诱导的水肿在15分钟时明显，在用IL - 1β（0.64±0.06 ml）或TNFα（0.47±0.05 ml）处理后60分钟和30分钟分别达到最大值，在360分钟时减轻。B1拮抗剂去 - 精氨酸9 - NPC 17731（1 - 30 nmol），而非B2拮抗剂Hoe 140（10 nmol），能显著抑制去 - 精氨酸9 - 缓激肽诱导的爪部水肿。地塞米松（0.5 mg/kg，皮下注射，4小时）或放线菌酮（1.5 mg/kg，皮下注射，6小时）能显著预防用IL - 1β（81±5%和59±3%）或TNFα（78±4%和43±2%）处理的大鼠中由去 - 精氨酸9 - 缓激肽（100 nmol）引起的水肿。吲哚美辛（2 mg/kg，腹腔注射）或美洛昔康（3 mg/kg，腹腔注射），提前1小时，能显著减轻用IL - 1β（40±6%和69±8%）或TNFα（43±3%和53±9%）处理的大鼠中由去 - 精氨酸9 - 缓激肽（100 nmol）诱导的水肿。提示皮内注射IL - 1β或TNFα会导致B1受体介导的爪部水肿上调，这种效应对地塞米松、放线菌酮和环氧化酶途径敏感。
