Septic shock is a critical clinical condition with a high mortality rate. While complement is an important defense system against bacterial infection, many clinical observations suggest that activation of complement factors is associated with detrimental effects in septic shock, such as multiorgan damages and poor outcome. Direct or indirect inhibition of complement may provide new approaches in managing septic shock. In the present study, we used a model of complement depletion by injection of cobra venom factor (CVF) to investigate the role of complement in zymosan-induced septic shock in mice. The results showed that the low complement activity at the time of shock initiation raised the number of survivors, prevented liver enlargement and lowered the increase of serum markers for liver injury at the 48th hour. The elevated percentage of Ly6C+ cells in the peritoneal exudate (PE) was diminished as a result of CVF-pretreatment. Also, the degree of apoptosis in PE and spleen was inhibited in complement-depleted animals and the levels of IL-6 in PE and plasma were suppressed. At late period survivors did not develop liver dysfunction compared to mice untreated with CVF. Therefore, an understanding of the mechanisms involved in the activation of complement during sepsis is essential for introducing new rational therapies.
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