SUPPRESSION OF ALTERNATIVE COMPLEMENT PATHWAY ACTIVITY BY RADIOGRAPHIC CONTRAST-MEDIA

The authors examined the effect of four different kinds of contrast me dia (ionic/non-ionic, monomer/dimer) on the activation of the compleme nt (C) system (haemolytic activity and anaphylatoxin generation) in vi tro. In addition, the authors compared the effect of contrast media on inulin-mediated generation of the anaphylatoxin derivative C3a des Ar g in sera from urticarial reactors and their non-reacting controls. It was observed that the incubation of commercial iohexol, ioxaglate, io dixanol and meglumin amidotriz solutions in normal human serum (NHS) r esulted in a dose-dependent decrease in the haemolytic activity of the alternative C pathway. Contrary to expectations the contrast media di d not activate C in NHS. Instead, inulin-induced generation of C3a des Arg was inhibited by all the four contrast media. The strongest inhib itor was ioxaglate, an ionic dimer. No significant difference between the urticarial reactors and non-reactors in the inhibition of C3a des Arg generation was observed. In analyzing the mechanism of C inhibitio n we found that the contrast media solutions, particularly the ionic o nes, prevented formation of the alternative pathway C3 convertase, C3b Bb, by inhibiting the binding of factor B to surface-associated C3b mo lecules. The results suggest that the previously observed decrease in haemolytic C titres by contrast media is due to direct suppression of C activity rather than activation-induced consumption.