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The Volatile anesthetics halothane and isoflurane differentially modulate pro-inflammatory cytokines-induced p38 mitogen-activated protein kinase activation

Itoh, T., Hirota, K., Hisano, T., Namba, T. and Fukuda, K.

J. Anesth, vol.18, pp203-209
DOI: 10.1007/s00540-004-0237-5

Abstract
Purpose
Volatile anesthetics affect the cardiovascular and immune systems. Toward a better understanding of the molecular mechanisms behind the modulation we focused on effects of halothane and isoflurane on the activation of p38 mitogen-activated protein kinase (MAPK) which plays a critical role in the cellular responses to extracellular stimuli such as lipopolysaccharide (LPS) and proinflammatory cytokines including tumor necrosis factor (TNF ) and interleukin 1 (IL-1).

Methods
Human umbilical vein endothelial cells and the established cell line HeLa cells were examined with molecular biological methods. Cells were treated with pro-inflammatory compounds with or without the volatile anesthetics. p38 MAPK activation was investigated by Western blotting analysis with phosphospecific anti-p38 MAPK antibodies.
Results
Isoflurane activated p38 MAPK by itself, but halothane did not. Halothane or isoflurane augmented the LPS- and TNF-induced activation of p38 MAPK. In contrast, neither halothane nor isoflurane did enhance p38 MAPK activation induced by IL-1. Neither of the anesthetics did affect H2O2- or MKK3-induced p38 MAPK activation.
Conclusion
Our in vitro results indicate that the volatile anesthetics used in the clinical field and animal experiments modify the p38 MAPK signaling cascade and suggest that target molecules of the anesthetics are not unique and the anesthetics regulate them differentially in clinically relevant doses.