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: Experimen tal animal study. Setting: Central animal laboratory of a university h ospital. Subjects: Twenty-five CB-deficient B2D10/Old and 25 CB-suffic ient B2D1O/New mice. Interventions: On day 0, all mice received an int raperitoneal 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 con dition) were measured daily and mortality was monitored. Clinical cond ition 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 we re killed and relative organ weights of lungs, liver, spleen, and kidn eys were calculated. Relative organ weight was defined as (organ weigh t/body weight) x 100%. Zymosan administration induced a typical tripha sic 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 CB-deficient mic e (p < .005). In the late phase, no differences could be noticed in th e courses of these biological parameters. Overall mortality was 2 (8%) of 25 in CB-deficient mice and 8 (32%) of 25 in C5-sufficient mice (p = .049), a difference that was mainly due to a difference in the acut e 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, defici ency of C5 could not prevent organ damage in the late multiple organ d ysfunction syndrome phase. This finding suggests that other factors mu st be more important in the development of the inflammatory response l eading to multiple organ dysfunction syndrome.