Deficiency of complement factor C5 reduces early mortality but does not prevent organ damage in an animal model of multiple organ dysfunction syndrome.

OBJECTIVE To evaluate the role of complement factor C5 in a model of zymosan-induced multiple organ dysfunction syndrome. DESIGN Experimental animal study. SETTING Central animal laboratory of a university hospital. SUBJECTS Twenty-five C5-deficient B2D10/Old and 25 C5-sufficient B2D10/New mice. INTERVENTIONS On day 0, all mice received an intraperitoneal injection with zymosan suspended in paraffin in a dose of 1 mg/g body weight. MEASUREMENTS AND MAIN RESULTS Between days 0 and 12, biological parameters (temperature, body weight, and clinical condition) were measured daily and mortality was monitored. Clinical condition was assessed as a symptom score by blindly grading the degree of lethargy, conjunctivitis, diarrhea, and ruffled fur of each mouse on a 2-point scale (maximum score of 4). On day 12, all surviving mice were killed and relative organ weights of lungs, liver, spleen, and kidneys were calculated. Relative organ weight was defined as (organ weight/body weight) x 100%. Zymosan administration induced a typical triphasic illness. Deterioration of the clinical condition, as indicated by the symptom score, and the decrease in temperature and body weight in the acute phase were all significantly less severe in C5-deficient mice (p < .005). In the late phase, no differences could be noticed in the courses of these biological parameters. Overall mortality was 2 (8%) of 25 in C5-deficient mice and 8 (32%) of 25 in C5-sufficient mice (p = .049), a difference that was mainly due to a difference in the acute phase. Organ damage, assessed as the relative organ weights, did not show any statistical differences for any organ between both strains. CONCLUSIONS Complement factor C5 appears to play an important role in the acute hyperdynamic septic response in this model. However, deficiency of C5 could not prevent organ damage in the late multiple organ dysfunction syndrome phase. This finding suggests that other factors must be more important in the development of the inflammatory response leading to multiple organ dysfunction syndrome.