Effects of ketamine on endotoxin-induced proinflammatory cytokine production and NF-?B activation in rat
- VernacularTitle:氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响
- Author:
Jie SUN
;
Zhiqiang ZHOU
;
Manlin DUAN
- Publication Type:Journal Article
- Keywords:
Ketamine;
Toxemia;
Inflammation mediators;
NF-kappa B
- From:
Chinese Journal of Anesthesiology
1994;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of ketamine on endotoxin-induced production of proinflammatory cytokines (IL-6, TNF-?) and activation of their modulating factor NF-?B in rat. Methods Thirty-six adult male Wistar rats weighing 250-300 g were randomly divided into 4 groups : (Ⅰ Ⅰ ) control group ( n = 6) ; (Ⅱ) endotoxin group received intravenous endotoxin ( Escherichia coli O111: B4)5mg?kg-1(n = 6); (Ⅲ) ketamine group received ketamine 50 mg?kg-1 ? h-1 i.v. (n = 6) and (Ⅳ) endotoxin + ketamine group received ketamine 0.5 or 5 or 50 mg?kg-1 ? h-1 after endotoxin ( n = 18 ) . The animals were anesthetized with urethane i. p. (1 g?kg-1) . Carotid artery was cannulated for BP and HR monitoring and jugular vein was cannulated for fluid or drug administration. Two hours after endotoxin administration the animals were sacrificed by exsanguination. Blood was collected and peripheral blood monocytes (PBMC) were isolated. NF-icB content in PBMC was measured by EMSA and plasma TNF-? and IL-6 concentrations were determined by ELISA. Results Progressive hypotension and tachycardia developed after endotoxin administration. Endotoxin also increased NF-icB content in PBMCs and plasma TNF-? and IL-6 concentrations. Ketamine 50 mg?kg-1 attenuated the endotoxin-induced hemodynamic response. Ketamine (0.5, 5, 50 mg?kg-1?h-1 ) suppressed NF-?B content in PBMC and inhibited plasma TNF-? level but plasma IL-6 level was not affected. Conclusion Ketamine can suppress endotoxin-induced NF-kappa B activation. Subanesthetic dose of ketamine has anti-inflammatory action.
