Increased Susceptibility to Septic and Endotoxic Shock in Monocyte Chemoattractant Protein 1/cc Chemokine Ligand 2-deficient Mice Correlates With Reduced Interleukin 10 and Enhanced Macrophage Migration Inhibitory Factor Production

Shock. 2006 Nov;26(5):457-63. doi: 10.1097/01.shk.0000228801.56223.92.

Abstract

The chemokine monocyte chemoattractant protein 1/CC chemokine ligand 2 (MCP-1/CCL2) is a potent chemoattractant of mononuclear cells and a regulatory mediator involved in a variety of inflammatory diseases. In the present study, we demonstrate that mcp-1/ccl2-deficient mice are more susceptible to systemic inflammatory response syndrome induced by lipopolysaccharide and to polymicrobial sepsis induced by cecum ligation and puncture (CLP) when compared with wild-type mice. Interestingly, in the CLP model, mcp-1/ccl2-deficient mice efficiently cleared the bacteria despite an impaired recruitment of leukocytes, especially mononuclear cells. The increased lethality rate in these models correlates with an impaired production of interleukin (IL) 10 in vivo. Furthermore, macrophages from mcp-1/ccl2-deficient mice activated with lipopolysaccharide also produced lower amounts of IL-10 and similar tumor necrosis factor compared with wild-type mice. We observed a drastic increase in the amounts of macrophage migration inhibitory factor at 6 and 24 h after CLP in mcp-1/ccl2-deficient mice. These results indicate that endogenous MCP-1/CCL2 positively regulates IL-10 but negatively controls macrophage migration inhibitory factor during peritoneal sepsis, thus suggesting an important immunomodulatory role for MCP-1/CCL2 in controlling the balance between proinflammatory and anti-inflammatory factors in sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cecum / surgery
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Interleukin-10 / metabolism*
  • Intramolecular Oxidoreductases
  • Leukocytes / pathology
  • Ligation
  • Lipopolysaccharides
  • Macrophage Migration-Inhibitory Factors / metabolism*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Peritonitis / genetics
  • Peritonitis / metabolism
  • Peritonitis / microbiology
  • Shock, Septic / genetics*
  • Shock, Septic / metabolism*
  • Shock, Septic / mortality
  • Systemic Inflammatory Response Syndrome / genetics
  • Systemic Inflammatory Response Syndrome / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Lipopolysaccharides
  • Macrophage Migration-Inhibitory Factors
  • Interleukin-10
  • Intramolecular Oxidoreductases
  • Mif protein, mouse