2 CHEMOTACTIC FACTORS, C5A AND MIP-1-ALPHA, DRAMATICALLY ALTER THE MORTALITY FROM ZYMOSAN-INDUCED MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS) - C5A CONTRIBUTES TO MODS WHILE MIP-1-ALPHA HAS A PROTECTIVE ROLE

Multiple organ dysfunction syndrome (MODS) is a major cause of morbidi ty and mortality in surgical intensive care units. It is characterized by progressive failure of two or more organs remote from the origin o f injury. Since MODS results from a severe generalized inflammatory re sponse, both chemokines and complement have had a proposed role in its pathophysiology. The availability of macrophage inflammatory protein 1 alpha (MIP-1 alpha) knockout mice and congenic C5-deficient and C5-s ufficient mice allowed us to investigate the individual contribution o f these immune modulators in MODS. It has been demonstrated in this as say that MIP-1 alpha has a protective role against MODS mortality, whi le C5a contributes to MODS mortality. Using a zymosan-induced MODS mur ine model, the absence of MIP-1 alpha increased mortality four-fold, w hereas the absence of C5 decreased mortality four-fold. Therefore, MIP -1 alpha-dependent mediators are essential in the prevention of MODS r elated deaths, while C5-dependent mediators of inflammation can be con sidered to be contributing to the development of MODS related deaths. (C) 1997 Elsevier Science Ltd.