[SB203580 reduces proinflammatory cytokine production in rats after cardiopulmonary bypass].
OBJECTIVE
To examine the changes in P38MAPK during and after cardiopulmonary bypass (CPB) and the effect of SB203580, a specific P38MAPK inhibitor, on CPB-induced pulmonary inflammatory response.


METHODS
Fifty-four SD rats were randomized into 3 groups (each=18), namely sham CPB group, CPB group, and SB203580 group in which rats underwent CPB with SB203580 pretreatment. The lungs were excised immediately after the rats were sacrificed at scheduled time points and p38, nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were detected.


RESULTS
The activities of P38 MAPK and NF-kappaB were significantly increased in CPB group as compared with those in sham CPB group. CPB resulted in increased TNF-alpha and IL-1beta production in the lung tissues. Administration of SB203580 prevented up-regulation of lung phosphorylated P38 MAPK, and decreased proinflammatory cytokine productions in the lung tissues.


CONCLUSIONS
P38 MAPK is activated in the lung tissue during and after CPB to affect the activation of NF-kappaB in the lung; SB203580 selectively inhibits P38 MAPK activation to reduce proinflammatory cytokine production after CPB.
Dong
Xiao
X
Department of Cardiothoracic Surgery, Second Affiliated Hospital, Nanchang University, Nanchang 330006, China. dongshi22000@yahoo.com.cn
Xu
Jian-Jun
JJ
He
Xiong
X
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis*; D007093:Imidazoles / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007093:Imidazoles; D053583:Interleukin-1beta; D016328:NF-kappa B; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580