title: MCP-1 protects mice in lethal endotoxemia.
abstract: The overzealous production of proinflammatory cytokines in sepsis can result in shock, multiorgan dysfunction, and even death. In this study, we assessed the role of monocyte chemoattractant protein-1 (MCP-1) as a mediator of sepsis in endotoxin-challenged mice. Intraperitoneal administration of LPS to CD-1 mice induced a substantial time-dependent increase in MCP-1 in plasma, lung, and liver. The passive immunization of mice with rabbit antimurine MCP-1 antiserum 2 h before endotoxin administration resulted in a striking increase in LPS-induced mortality from 10% in control animals to 65% in anti-MCP-1-treated animals. Importantly, the administration of anti-MCP-1 antibodies to endotoxin-challenged mice resulted in increases in peak TNF-alpha and IL-12 levels, and also in a trend toward decreased serum levels of IL-10. Conversely, the administration of recombinant murine MCP-1 intraperitoneally significantly protected mice from endotoxin-induced lethality, and resulted in an increase in IL-10 levels, a decrease in IL-12 levels, and a trend toward decreased levels of TNF. In conclusion, our findings indicate that MCP-1 is a protective cytokine expressed in murine endotoxemia, and does so by shifting the balance in favor of antiinflammatory cytokine expression in endotoxin-challenged animals.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Michigan Medical School, Ann Arbor, Michigan 48109-0360, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Zisman
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: W C
authors.initials: WC
authors.lastname: Tsai
authors.forename: K
authors.initials: K
authors.lastname: Bucknell
authors.forename: J
authors.initials: J
authors.lastname: Wilkowski
authors.forename: T J
authors.initials: TJ
authors.lastname: Standiford
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology / Q000502:physiology* / Q000627:therapeutic use; D019446:Endotoxemia / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D007116:Immunization, Passive; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12