Role of the complement in experimental sepsis

ment activation products and relevant receptors were stressed in the setting of experimental sepsis [cecal ligation and puncture (CLP)] in mice and rats. In addition, some limited evidence was pre-sented related to humans with septic shock (requir-ing vasopressor support). Collectively, the data suggested that events found in CLP also occur in human sepsis. Experimental sepsis (CLP) in ro-dents is associated with robust complement con-sumption and appearance of activation products (C3a, C5a) in plasma. During sepsis, there is up-regulation of C5a receptors (C5aR, C5L2) on blood polymorphonuclear neutrophils (PMNs) and in lungs, liver, kidneys, and heart. CLP also leads to dramatic reductions of C5aRs on blood PMNs, the intensity of which correlates with lethality. In-terception in vivo of C5a or C5aR dramatically improves survival after CLP, preserves innate im-mune functions of blood PMNs, and greatly atten-uates the intensity of consumptive coagulopathy and activation of the fibrinolytic system after CLP. In humans with septic shock, there is evidence of complement activation products in plasma along with loss of C5aRs on blood PMNs. These data suggest that in septic humans, interception of C5a or C5aR might be clinically efficacious. J. Leukoc