Role of IL-10 in regulating proinflammatory cytokine release by Kupffer cells following trauma-hemorrhage

Yukihíro Yokoyama, William C. Kitchens, Balazs Toth, Martin G. Schwacha, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

IL-6 and TNF-α production by Kupffer cells is markedly stimulated following trauma-hemorrhage (T-H). Because IL-10 is an anti-inflammatory cytokine, the aim of this study was to determine whether IL-10 regulates Kupffer cell proinflammatory cytokine release following T-H. To study this, we subjected adult male Sprague-Dawley rats to sham operation or T-H. The procedure involved a 5-cm midline laparotomy and ∼90 min of hemorrhagic shock (35 mmHg), followed by resuscitation with four times the shed blood volume in the form of Ringer's lactate. At 2 h after the end of resuscitation, livers were perfused in vitro and perfusate was collected. In separate studies, Kupffer cells were isolated and incubated with different concentrations of anti-IL-10 MAb. IgG was used as control. After 16 h of incubation, IL-6 and TNF-α levels were measured by ELISA. Plasma IL-10 levels increased significantly following T-H. IL-10 levels in the perfusate and IL-10 production by cultured Kupffer cells were also significantly higher in the T-H group. When Kupffer cells were incubated with 10 μg/ml of anti-IL-10 MAb, IL-6 and TNF-α production were significantly increased in both sham and T-H groups compared with those not treated with anti-IL-10 MAb. However, these changes were not observed when the cells were incubated with irrelevant (control) IgG. These results indicate that IL-10 production by Kupffer cells early after T-H may play a pivotal role in attenuating the proinflammatory cytokine environment, possibly in an autocrine/paracrine manner.

Original languageEnglish (US)
Pages (from-to)G942-G946
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume286
Issue number6 49-6
DOIs
StatePublished - Jun 2004

Keywords

  • Anti-inflammatory cytokine
  • Anti-interleukin-10 antibodies
  • Isolated liver perfusion

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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