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Interleukin-10 mediates the protective effect of Linomide by reducing CXC chemokine production in endotoxin-induced liver injury

Li, Xiang LU ; Klintman, Daniel LU ; Sato, T; Hedlund, G; Schramm, R; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2004) In British Journal of Pharmacology 143(7). p.865-871
Abstract
1 The immunomodulator Linomide has been shown to protect against septic liver injury by reducing hepatic accumulation of leukocytes although the detailed anti-inflammatory mechanisms remain elusive. This study examined the effect of Linomide on the production of CXC chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) and interleukin-10 (IL-10) in lipopolysaccharide (LPS)/D-galactosamine (Gal)-induced liver injury in mice. 2 It was found that pretreatment with 300 mg kg(-1) of Linomide markedly Suppressed leukocyte recruitment, perfusion failure, and hepatocellular damage and apoptosis in the liver of endotoxemic mice. 3 Administration of Linomide inhibited endotoxin-induced... (More)
1 The immunomodulator Linomide has been shown to protect against septic liver injury by reducing hepatic accumulation of leukocytes although the detailed anti-inflammatory mechanisms remain elusive. This study examined the effect of Linomide on the production of CXC chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) and interleukin-10 (IL-10) in lipopolysaccharide (LPS)/D-galactosamine (Gal)-induced liver injury in mice. 2 It was found that pretreatment with 300 mg kg(-1) of Linomide markedly Suppressed leukocyte recruitment, perfusion failure, and hepatocellular damage and apoptosis in the liver of endotoxemic mice. 3 Administration of Linomide inhibited endotoxin-induced gene expression of MIP-2 and KC and significantly reduced the hepatic production of MIP-2 and KC by 63 and 80%, respectively. Moreover, it was found that Linomide increased the liver content of IL-10 by more than three-fold in endotoxemic mice. 4 The protective effect of Linomide against endotoxin-induced inflammation and liver injury was abolished in IL-10-deficient mice, suggesting that the beneficial effect of Linomide is dependent on the function of IL-10. 5 Taken together, these novel findings suggest that the protective effect of Linomide is mediated via local upregulation of IL-10, which in turn decreases the generation of CXC chemokines and pathological recruitment of leukocytes in the liver of endotoxemic mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
intravital microscopy, endotoxin, adhesion, chemokines, sepsis, Linomide
in
British Journal of Pharmacology
volume
143
issue
7
pages
865 - 871
publisher
The British Pharmacological Society
external identifiers
  • wos:000225491300007
  • pmid:15492015
  • scopus:10844296610
ISSN
1476-5381
DOI
10.1038/sj.bjp.0706015
language
English
LU publication?
yes
id
16469d95-f239-46b3-b778-63bb8872e55a (old id 259756)
date added to LUP
2007-10-24 18:29:15
date last changed
2017-05-28 04:16:16
@article{16469d95-f239-46b3-b778-63bb8872e55a,
  abstract     = {1 The immunomodulator Linomide has been shown to protect against septic liver injury by reducing hepatic accumulation of leukocytes although the detailed anti-inflammatory mechanisms remain elusive. This study examined the effect of Linomide on the production of CXC chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) and interleukin-10 (IL-10) in lipopolysaccharide (LPS)/D-galactosamine (Gal)-induced liver injury in mice. 2 It was found that pretreatment with 300 mg kg(-1) of Linomide markedly Suppressed leukocyte recruitment, perfusion failure, and hepatocellular damage and apoptosis in the liver of endotoxemic mice. 3 Administration of Linomide inhibited endotoxin-induced gene expression of MIP-2 and KC and significantly reduced the hepatic production of MIP-2 and KC by 63 and 80%, respectively. Moreover, it was found that Linomide increased the liver content of IL-10 by more than three-fold in endotoxemic mice. 4 The protective effect of Linomide against endotoxin-induced inflammation and liver injury was abolished in IL-10-deficient mice, suggesting that the beneficial effect of Linomide is dependent on the function of IL-10. 5 Taken together, these novel findings suggest that the protective effect of Linomide is mediated via local upregulation of IL-10, which in turn decreases the generation of CXC chemokines and pathological recruitment of leukocytes in the liver of endotoxemic mice.},
  author       = {Li, Xiang and Klintman, Daniel and Sato, T and Hedlund, G and Schramm, R and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1476-5381},
  keyword      = {intravital microscopy,endotoxin,adhesion,chemokines,sepsis,Linomide},
  language     = {eng},
  number       = {7},
  pages        = {865--871},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Interleukin-10 mediates the protective effect of Linomide by reducing CXC chemokine production in endotoxin-induced liver injury},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0706015},
  volume       = {143},
  year         = {2004},
}