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

Martin G. Schwacha, Christian P. Schneider, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The activation of a macrophage (Mφ)-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 anti-inflammatory cytokine that can downregulate Mφ activity, has also been implicated in postburn immune dysfunction, its role in the regulation of Mφ 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 Mφs were isolated 7 days later. Lipopolysaccharide (LPS)-stimulated IL-10, IL-6, tumor necrosis factor (TNF)-α, 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-α release, but not NO release, in both groups. The addition of exogenous IL-10 to the Mφ 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, Mφs from injured mice were significantly better able to maintain inflammatory mediator-productive capacity. The resistance of Mφs 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 Mφs, following thermal injury, display resistance to suppression by IL-10 due in part to downregulation of IL-10R expression.

Original languageEnglish (US)
Pages (from-to)C1180-C1187
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number4 50-4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Immunosuppression
  • Interleukin-10 receptor
  • Interleukin-6
  • Nitric oxide
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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