We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Interleukin-10 mediates the protective effect of Linomide by reducing CXC chemokine production in endotoxin-induced liver injury.
- Authors
Li, Xiang; Klintman, Daniel; Sato, Tohru; Hedlund, Gunnar; Schramm, René; Jeppsson, Bengt; Thorlacius, Henrik; Schramm, René
- Abstract
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. 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. 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. 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. 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.
- Subjects
INTERLEUKIN-10; ENDOTOXINS; LIVER diseases; IMMUNOLOGICAL adjuvants; LEUCOCYTES; GROWTH factors; MICROBIAL lipids
- Publication
British Journal of Pharmacology, 2004, Vol 143, Issue 7, p865
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0706015