Two chemotactic factors, C5a and MIP-1alpha, dramatically alter the mortality from zymosan-induced multiple organ dysfunction syndrome (MODS): C5a contributes to MODS while MIP-1alpha has a protective role.
Multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in surgical intensive care units. It is characterized by progressive failure of two or more organs remote from the origin of injury. Since MODS results from a severe generalized inflammatory response, both chemokines and complement have had a proposed role in its pathophysiology. The availability of macrophage inflammatory protein 1 alpha (MIP-1alpha) knockout mice and congenic C5-deficient and C5-sufficient mice allowed us to investigate the individual contribution of these immune modulators in MODS. It has been demonstrated in this assay that MIP-1alpha has a protective role against MODS mortality, while C5a contributes to MODS mortality. Using a zymosan-induced MODS murine model, the absence of MIP-1alpha increased mortality four-fold, whereas the absence of C5 decreased mortality four-fold. Therefore, MIP-1alpha-dependent mediators are essential in the prevention of MODS related deaths, while C5-dependent mediators of inflammation can be considered to be contributing to the development of MODS related deaths.
Miller
C G
CG
Department of Microbiology and Immunology, University of Louisville, School of Medicine, KY 40292, U.S.A.
Cook
D N
DN
Kotwal
G J
GJ
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors / Q000494:pharmacology*; D015936:Complement C5a / Q000494:pharmacology*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D008107:Liver Diseases / Q000188:drug therapy / Q000401:mortality; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D008206:Lymphatic Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000139:chemically induced* / Q000188:drug therapy / Q000401:mortality*; D013577:Syndrome; D015054:Zymosan / Q000819:agonists / Q000037:antagonists & inhibitors / Q000633:toxicity*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D019402:Macrophage Inflammatory Proteins; D015936:Complement C5a; D015054:Zymosan