Resistance of macrophages to the suppressive effect of interleukin-10 following thermal injury

被引:35
|
作者
Schwacha, MG [1 ]
Schneider, CP [1 ]
Bland, KI [1 ]
Chaudry, IH [1 ]
机构
[1] Univ Alabama Birmingham, Dept Surg, Surg Res Ctr, Birmingham, AL 35294 USA
来源
关键词
interleukin-10; receptor; interleukin-6; tumor necrosis factor-alpha; nitric oxide; immunosuppression;
D O I
10.1152/ajpcell.2001.281.4.C1180
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The activation of a macrophage (M phi)-dependent proinflammatory cascade following thermal injury plays an important role in the development of immunosuppression and increased susceptibility to subsequent sepsis in burn patients. In contrast, although interleukin (IL)-10, an antiinflammatory cytokine that can downregulate M phi activity, has also been implicated in postburn immune dysfunction, its role in the regulation of M phi function postburn remains unclear. To study this, C57BL/6 female mice were subjected to a 25% total body surface area third-degree scald burn, and splenic M phi s were isolated 7 days later. Lipopolysaccharide (LPS)-stimulated IL-10, IL-6, tumor necrosis factor (TNF)-alpha, and nitric oxide (NO) production were significantly increased in the burn group compared with shams. Blockade of endogenous IL-10 activity enhanced IL-6 and TNF-a release, but not NO release, in both groups. The addition of exogenous IL-10 to the M phi cultures dose dependently suppressed production of these inflammatory mediators in both groups. The timing of IL-10 addition to the cultures in relation to LPS stimulation, however, was critical. The suppressive effect of exogenous IL-10 was attenuated in both groups when the cells were exposed to IL-10 at 4-6 h after LPS stimulation; however, M phis from injured mice were significantly better able to maintain inflammatory mediator-productive capacity. The resistance of M phis from injured mice to IL-10-mediated suppression correlated with decreased IL-10 receptor (IL-10R) expression and increased CD11b expression. These findings suggest that M phis, following thermal injury, display resistance to suppression by IL-10 due in part to downregulation of IL-10R expression.
引用
收藏
页码:C1180 / C1187
页数:8
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