TY - JOUR
T1 - Endogenous MCP-1 influences systemic cytokine balance in a murine model of acute septic peritonitis
AU - Matsukawa, Akihiro
AU - Hogaboam, Cory M.
AU - Lukacs, Nickolas W.
AU - Lincoln, Pamela M.
AU - Strieter, Robert M.
AU - Kunkel, Steven L.
N1 - Funding Information:
This work was supported in part by National Institutes of Health Grants P50HL60289 and HL31237. The authors thank Ms. Holly Evanoff for her excellent technical assistance.
PY - 2000/4
Y1 - 2000/4
N2 - Sepsis and septic syndrome represent an intense systemic response with multiple physiologic and immunologic abnormalities, leading to multiple organ failure. Recent investigations suggest that the critical conditions are balanced by endogenous cytokines. In the present study, we examined the involvement of endogenous monocyte chemoattractant protein (MCP)-1 in the regulation of cytokine production in tissue/organs in a murine model of acute septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies showed that CLP induced elevated levels of MCP-1 in tissues, such as liver, lung, and kidney. To neutralize endogenous MCP-1, either anti-MCP-1 antibodies or control antibodies were intraperitoneally administered 2 h prior to CLP. Administration of anti-MCP-1 antibodies resulted in a decrease in the level of interleukin (IL)-13 in tissues, while increasing the level of tumor necrosis factor-α, compared to control. In addition, anti-MCP-1 treatment decreased the level of IL-12 and, in contrast, increased the level of IL-10 in specific tissues. These findings suggest that endogenous MCP-1 influences the cytokine balance in tissues in favor of antiinflammatory and immune-enhancing cytokines, probably protecting the host from tissue/organ damage during sepsis. (C) 2000 Academic Press.
AB - Sepsis and septic syndrome represent an intense systemic response with multiple physiologic and immunologic abnormalities, leading to multiple organ failure. Recent investigations suggest that the critical conditions are balanced by endogenous cytokines. In the present study, we examined the involvement of endogenous monocyte chemoattractant protein (MCP)-1 in the regulation of cytokine production in tissue/organs in a murine model of acute septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies showed that CLP induced elevated levels of MCP-1 in tissues, such as liver, lung, and kidney. To neutralize endogenous MCP-1, either anti-MCP-1 antibodies or control antibodies were intraperitoneally administered 2 h prior to CLP. Administration of anti-MCP-1 antibodies resulted in a decrease in the level of interleukin (IL)-13 in tissues, while increasing the level of tumor necrosis factor-α, compared to control. In addition, anti-MCP-1 treatment decreased the level of IL-12 and, in contrast, increased the level of IL-10 in specific tissues. These findings suggest that endogenous MCP-1 influences the cytokine balance in tissues in favor of antiinflammatory and immune-enhancing cytokines, probably protecting the host from tissue/organ damage during sepsis. (C) 2000 Academic Press.
KW - Cytokine balance
KW - Monocyte chemoattractant protein-1
KW - Multiple organ failure
KW - Sepsis
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U2 - 10.1006/exmp.1999.2296
DO - 10.1006/exmp.1999.2296
M3 - Article
C2 - 10716911
AN - SCOPUS:0034065513
SN - 0014-4800
VL - 68
SP - 77
EP - 84
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 2
ER -