P38 mitogen-activated protein kinase inhibition attenuates pulmonary inflammatory response in a rat cardiopulmonary bypass model

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Abstract
Lung injury secondary to cardiopulmonary bypass (CPB) is probably caused by a combination of ischemia–repefusion injury and systemic inflammatory response. The mechanisms that mediate lung injury after CPB are likely multiple and include inflammatory elements of leukocyte activation and proinflammatory cytokine release [1]. The p38 kinases are members of the mitogen-activated protein (MAP) kinases, which are important signal transducers. They modulate the production of proinfammatory cytokines (IL-1β, tumor necrosis factor (TNF)-α, IL-6, IL-8) and other mediators such as nitric oxide [2,3]. Several studies showed that p38 MAPK be activated during and after CPB [4], but the role of p38 MAPK activation in response to pulmonary inflammatory response after CPB remains unclear. NF-κB system is another major signaling pathway responsible for proinflammatory cytokine release after cardiopulmonary bypass [5]. Whether p38 MAP kinase can activate NF-κB directly remains controversial. Many studies suggested that p38 MAP kinase does not activate NF-κB directly in response to LPS or cytokines [6,7]. But Madrid et al. [8] found that the p38 MAP kinase promoted direct transactivation of NF-κB through IκB kinase. The relationship between p38 MAP kinase and NF-κB system in the proinflammatory cytokine release following cardiopulmonary bypass has not yet been addressed. In this study, we have examined the effect of SB203580, a specific p38 MAP kinase inhibitor, on CPB-induced pulmonary inflammatory response as well as the activation of NF-κB in rat CPB model, as to characterize the role of p38 MAP kinase in the pathogenesis of CPB-induced pulmonary inflammatory response.

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