Nonimmunologic complement activation in normal human serum induced by radiographic contrast media.

Area of Science:

• Immunology
• Pharmacology

Background:

• Radiographic contrast media (RCM) are essential diagnostic tools.
• Potential adverse effects of RCM, including complement activation, require investigation.

Purpose of the Study:

• To investigate the in vitro effects of iothalamate and iodipamide on human complement (C) system components.
• To determine the mechanism of RCM-induced complement activation.

Main Methods:

• In vitro incubation of RCM with normal, C2-deficient, and agammaglobulinemic human sera.
• Assays for hemolytic activity of complement components (C4, C2, C3, C5, C6, C8, C9).
• Immunoelectrophoresis to detect C3 cleavage products.
• In vitro incubation of purified C3 with RCM.
• Analysis of patient serum samples before and after intravenous pyelography.

Main Results:

• Iothalamate and iodipamide dose-dependently activated complement components, reducing hemolytic activity of C4, C2, C3, and C5, but not C6, C8, or C9.
• RCM induced C3 cleavage, evidenced by C3 fragments, even in the presence of EDTA, suggesting a non-convertase mechanism.
• Purified C3 was not directly altered by RCM.
• No significant changes in total hemolytic complement activity or C3 levels were observed in patients post-intravenous pyelography.

Conclusions:

• RCM can activate the complement system in vitro through a mechanism independent of classical and alternative pathway convertases.
• The in vitro complement activation by RCM does not appear to directly involve C3 molecule alteration.
• Clinical administration of RCM during intravenous pyelography did not result in detectable changes in complement activity in patients.