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Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent.

Publication ,  Journal Article
Camargo, CA; Madden, JF; Gao, W; Selvan, RS; Clavien, PA
Published in: Hepatology
December 1997

Interleukin-6 (IL-6) is an acute reactant cytokine with anti-inflammatory properties, which has been found to prevent injury in a model of acute hepatitis in mice through downregulation of tumor necrosis factor alpha (TNF-alpha); to correlate inversely with markers of hepatocellular injury in patients with liver ischemia; and to initiate liver regeneration in mice. In this study, we investigated the role of IL-6 in rodent models of hepatic warm ischemia/reperfusion (WI/Rp) injury. IL-6-deficient mice (-/-) were subjected to hepatic WI and compared with C57BL/6 mice, as well as IL-6 -/- mice pretreated with recombinant IL-6 (rIL-6). The effects of rIL-6 following various periods of ischemia were further studied in models of hepatic ischemia in rats. IL-6 -/- mice had increased reperfusion injury as assessed by transaminase levels and a tissue necrosis scoring system when compared with controls, an effect prevented by pretreatment with rIL-6. Similarly, rats pretreated with rIL-6 had reduced reperfusion injury and better survival than controls in each respective WI group. Tissue TNF-alpha expression measured by Northern blot analysis and serum C-reactive protein (CRP) levels, a marker of inflammation, were significantly reduced in animals pretreated with rIL-6. Administration of antibodies to TNF-alpha reproduced the beneficial effect of rIL-6. Hepatocyte proliferation, as assessed by a scoring method for mitotic index and proliferating nuclear cell antigen staining, was markedly increased in rIL-6-treated rats when compared with controls. In conclusion, this study suggests that IL-6 could play an important role in limiting hepatic warm ischemia/reperfusion (WI/Rp) injury, probably through its anti-inflammatory properties, modulation of TNF-alpha, and/or promotion of liver regeneration. rIL-6 might become an important cytokine in clinical situations associated with WI/Rp injury.

Duke Scholars

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

December 1997

Volume

26

Issue

6

Start / End Page

1513 / 1520

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Survival Rate
  • Reperfusion Injury
  • Recombinant Proteins
  • Rats, Wistar
  • Rats
  • RNA, Messenger
  • Proliferating Cell Nuclear Antigen
  • Neutrophils
  • Mice, Knockout
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Camargo, C. A., Madden, J. F., Gao, W., Selvan, R. S., & Clavien, P. A. (1997). Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatology, 26(6), 1513–1520. https://doi.org/10.1002/hep.510260619
Camargo, C. A., J. F. Madden, W. Gao, R. S. Selvan, and P. A. Clavien. “Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent.Hepatology 26, no. 6 (December 1997): 1513–20. https://doi.org/10.1002/hep.510260619.
Camargo CA, Madden JF, Gao W, Selvan RS, Clavien PA. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatology. 1997 Dec;26(6):1513–20.
Camargo, C. A., et al. “Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent.Hepatology, vol. 26, no. 6, Dec. 1997, pp. 1513–20. Pubmed, doi:10.1002/hep.510260619.
Camargo CA, Madden JF, Gao W, Selvan RS, Clavien PA. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatology. 1997 Dec;26(6):1513–1520.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

December 1997

Volume

26

Issue

6

Start / End Page

1513 / 1520

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Survival Rate
  • Reperfusion Injury
  • Recombinant Proteins
  • Rats, Wistar
  • Rats
  • RNA, Messenger
  • Proliferating Cell Nuclear Antigen
  • Neutrophils
  • Mice, Knockout