Suppressive effects of levobupivacaine on endotoxin-induced microglial activation.
BACKGROUND
We sought to elucidate the effects of levobupivacaine on modulating endotoxin-induced upregulation of inflammatory mediators and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways in activated microglia.


MATERIALS AND METHODS
Confluent murine microglia (BV-2) were treated with endotoxin (lipopolysaccharide, 50 ng/mL) or endotoxin plus levobupivacaine (5, 25, or 50 μM) and denoted as the LPS, LPS + L(5), LPS + L(25), and LPS + L(50) groups, respectively. Levobupivacaine was administered immediately after endotoxin. Control groups were run simultaneously.


RESULTS
The concentrations of inflammatory mediators, including macrophage inflammatory protein-2 (P = 0.023 and 0.016), tumor necrosis factor-α (P = 0.025 and 0.020), interleukin (IL)-1β (P = 0.018 and 0.014), IL-6 (P = 0.029 and 0.023), nitric oxide (P = 0.025 and 0.026), and prostaglandin E2 (P = 0.028 and 0.016) of the LPS + L(25) and LPS + L(50) groups were significantly lower than those of the LPS group. The concentrations of macrophage inflammatory protein-2 (P = 0.035), IL-1β (P = 0.024), nitric oxide (P = 0.031), and prostaglandin E2 (P = 0.036) but not tumor necrosis factor-α and interleukin-6 of the LPS + L(5) group were also significantly lower than those of the LPS group. These data revealed that effects of endotoxin on upregulating inflammatory mediators were inhibited by levobupivacaine. Moreover, effects of endotoxin on activating NF-κB, including inhibitor-κB degradation, NF-κB nuclear translocation, and NF-κB-DNA binding, were also inhibited by levobupivacaine. Similarly, effects of endotoxin on activating MAPKs, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAPK, were also significantly inhibited by levobupivacaine.


CONCLUSIONS
Levobupivacaine significantly inhibited endotoxin-induced upregulation of inflammatory mediators and activation of NF-κB and MAPKs signaling pathways in activated microglia.
['Huang|Ya-Hsien|YH|', 'Yen|Jiin-Cherng|JC|', 'Lee|Jie-Jen|JJ|', 'Liao|Jyh-Fei|JF|', 'Liaw|Wen-Jinn|WJ|', 'Huang|Chun-Jen|CJ|']
D000779:Anesthetics, Local D000818:Animals D002045:Bupivacaine D002460:Cell Line D054426:Chemokine CXCL2 D015232:Dinoprostone D004305:Dose-Response Relationship, Drug D004731:Endotoxins D053583:Interleukin-1beta D015850:Interleukin-6 D000077554:Levobupivacaine D008070:Lipopolysaccharides D051379:Mice D017628:Microglia D020929:Mitogen-Activated Protein Kinase Kinases D016328:NF-kappa B D009569:Nitric Oxide D015398:Signal Transduction D014409:Tumor Necrosis Factor-alpha
NF-κB MAPK Microglia LPS Chemokine Cytokine