The role of interleukin-10 in the regulation of the systemic inflammatory response following trauma-hemorrhage

Christian P. Schneider, Martin G. Schwacha, Irshad H. Chaudry

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Pro-inflammatory cytokine release after shock is central in the development of subsequent multiple organ dysfunction syndrome. Some studies suggest that interleukin-10 (IL-10) is an immunosuppressive mediator after injury or sepsis, while others suggest that IL-10 is an important regulator of the pro-inflammatory response. We hypothesized that in a model of trauma and hemorrhagic shock (TH), IL-10 regulates pro-inflammatory cytokine activity via an autocrine effect on cytokine mRNA transcription in Kupffer cells early after TH. To study this, male C3H/HeN mice were sham-operated or subjected to TH. Plasma levels of TNF-α, IL-6 and PGE2 were elevated following TH. A sharp peak in IL-10 levels was observed at 2 h after the insult. Kupffer cell (KC) depletion prior to TH reduced plasma IL-6, IL-10 and TNF-α levels, whereas treatment with anti-IL-10 after TH increased IL-6 and TNF-α levels. Kupffer cell mRNA expression for IL-6, IL-10 and TNF-α was elevated in the TH group and further increased by anti-IL-10 treatment. These findings indicate that KC-dependent IL-10 regulates the early systemic inflammatory response after TH. Thus, while IL-10 is an important mediator of immunosuppression following traumatic injury, it also is beneficial with regard to its ability to counter-regulate the early inflammatory response under such conditions.

Original languageEnglish (US)
Pages (from-to)22-32
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1689
Issue number1
DOIs
StatePublished - May 24 2004
Externally publishedYes

Keywords

  • Anti-IL-10
  • Cytokine
  • GdCl
  • Immune response
  • Kupffer cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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