Action of S 5682 on the complement system. In vitro and in vivo study

Activation of the complement system during the early phase of inflammation is partly responsible for increased vascular permeability, white blood cell margination and stimulation of phagocytosis. The aim of this study was to evaluate the anti-inflammatory action of S 5682 in terms of inactivation of the serum complement system. Serum complement was measured by the method of Mayer modified. In vitro, S 5682 was tested on human and rabbit sera with increasing concentrations from 10 to 5.10(-8) g in the presence of different complement pathways activators. In vivo, serum anticomplement activity was evaluated is the N.Z. rabbit after administration of a single dose (100 mg/kg) of S 5682. In vitro, the anticomplement action of S 5682 was effective, starting at the concentration 1.10(-9) g for both classical (IC50 = 6.19.10(-9) g) and alternative pathways (IC50 = 7.69.10(-9) g). This dose-dependent anticomplement action was statistically significant (p less than 0.01) and involved fraction Clq and C3. In vivo, there was a statistically significant decrease (p less than 0.01) of complement activation which reached a maximum of 74%, 180 minutes after the administration of S 5682. This decrease was still significant after 5 hours (p greater than 0.01). These data suggest that the anti-oedematous effect of S 5682 can be partly explained by anti-inflammatory properties in relation with an anticomplement action.