Brefeldin A inhibits experimentally induced AA amyloidosis

Brefeldin A, an antibiotic with effects on certain intracellular compartments, was tested on murine secondary AA amyloidosis. Effects on splenic proteoglycan metabolism were analyzed along with plasma serum amyloid A (SAA) levels.

Brefeldin A was administered daily to mice undergoing inflammatory stimulation with complete Freund's adjuvant to induce reactive AA amyloidosis. AA amyloid deposition was assessed using histochemistry, immunohistochemistry, and electron microscopy. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting were used to detect SAA in acute phase serum. Relative (semiquantitative) measurements of total SAA levels were obtained by densitometry of stained gels. Splenic proteoglycan metabolism was analyzed in treated animals and compared to untreated individuals by in vivo 35S administration during amyloid fibrillogenesis.

Based on (immuno)histochemistry and electron microscopy, animals undergoing drug treatment did not develop splenic amyloidosis, whereas the control animals exhibited massive amyloid fibril deposits in the spleen (p < 0.001). SAA was detected at roughly equal quantities in serum from both groups. No significant qualitative or quantitative difference in proteoglycan synthesis was found.

Brefeldin A seems to exert an inhibitory action on murine AA amyloidosis. It appears that the effect does not depend on the lack of fibril protein precursor nor altered proteoglycan synthesis.