Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression

被引:40
作者
Kadokami, T
McTiernan, CF
Kubota, T
Frye, CS
Bounoutas, GS
Robbins, PD
Watkins, SC
Feldman, AM
机构
[1] UPMC Hlth Syst, Cardiovasc Inst, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Med Ctr, Ctr Biol Imaging, Pittsburgh, PA 15213 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2001年 / 280卷 / 05期
关键词
adenovirus; chemokine; endotoxin shock; tumor necrosis factor-alpha;
D O I
10.1152/ajpheart.2001.280.5.H2281
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Tumor necrosis factor (TNF)-alpha plays a key role in the pathogenesis of septic shock syndrome, and myocardial TNF-alpha expression may contribute to this pathophysiology. We examined the myocardial expression of TNF-alpha -related cytokines and chemokines in mice exposed to lipopolysaccharide (LPS) and tested the effects of anti-TNF therapy on myocardial cytokine expression. Cytokine mRNA levels were measured by RNase protection assay, and protein levels in the plasma and myocardium were assessed by enzyme-linked immunosorbent assays. LPS (4 mug/g body wt ip) induced marked cytokine expression, including TNF-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemotactic protein (MCP)-1, in both the plasma and myocardium. Pretreatment with adenovirus-mediated TNF receptor fusion protein (AdTNFR1; 10(9) plaque-forming units iv) decreased plasma cytokine levels. In contrast, whereas myocardial IL-1 beta expression was also suppressed, expression of IL-6 and MCP-1 was not inhibited by AdTNFR1. In summary, anti-TNF treatment differentially altered the cytokine expression in the plasma and myocardium during endotoxemia. Inability to block myocardial expression of IL-6 and MCP-1 suggests a possible mechanism for the failure of anti-TNF therapies in the treatment of endotoxin shock.
引用
收藏
页码:H2281 / H2291
页数:11
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