Suppression of alternative complement pathway activity by radiographic contrast media

Area of Science:

• Immunology
• Biochemistry

Background:

• Contrast media are widely used in medical imaging.
• Their potential effects on the complement (C) system, particularly the alternative pathway, are not fully understood.
• Previous studies suggested contrast media might activate the C system.

Purpose of the Study:

• To investigate the in vitro effects of four different contrast media on complement system activation.
• To compare the impact of contrast media on anaphylatoxin generation in individuals with and without a history of urticarial reactions.
• To elucidate the mechanism by which contrast media influence complement activity.

Main Methods:

• In vitro incubation of normal human serum (NHS) with four contrast media (iohexol, ioxaglate, iodixanol, meglumin amidotrizoate).
• Assay of haemolytic activity of the alternative C pathway.
• Measurement of inulin-induced generation of C3a des Arg in sera from urticarial reactors and controls.
• Analysis of the alternative pathway C3 convertase formation.

Main Results:

• All four contrast media caused a dose-dependent decrease in alternative pathway haemolytic activity in NHS.
• Contrary to expectations, contrast media did not activate the complement system.
• Inulin-induced C3a des Arg generation was inhibited by all contrast media, with ionic dimers like ioxaglate showing the strongest effect.
• No significant difference in inhibition was observed between urticarial reactors and non-reactors.
• Contrast media, especially ionic ones, inhibited the formation of the alternative pathway C3 convertase (C3bBb) by preventing Factor B binding to C3b.

Conclusions:

• Contrast media do not activate the complement system in vitro.
• They directly suppress the alternative complement pathway activity.
• The observed decrease in haemolytic complement titres is likely due to direct inhibition, not activation-induced consumption.