Effect of colchicine on experimental amyloidosis in two CBA/J mouse models. Chronic inflammatory stimulation and administration of amyloid-enhancing factor during acute inflammation.
To investigate the mechanism of action of colchicine in blocking amyloid deposition, two model systems of amyloidosis in CBA/J mice were studied. In experimental chronic inflammation, daily injection of silver nitrate (AgNO3) resulted in the deposition of 667 +/- 68 ng of amyloid A protein (AA)/mg of spleen after 25 days. Treatment with 10 micrograms of colchicine daily decreased AgNO3-induced AA deposition to 12 +/- 1 ng of AA/mg of spleen (p less than 0.001). Colchicine diminished the acute phase serum amyloid A protein (SAA) response after 24 hours. Over a 25-day period, SAA concentrations declined and approached baseline both in colchicine-treated and (unexpectedly) in control mice. This suggested that suppression of SAA levels was not the primary event inhibiting amyloid deposition. In a model of accelerated amyloid deposition, injection of preformed amyloid-enhancing factor along with AgNO3 induced the deposition of 974 +/- 46 ng of AA/mg of spleen 48 hours later. Colchicine only partially decreased amyloid-enhancing factor-induced amyloid deposition to 578 +/- 91 ng of AA/mg of spleen, while blunting the acute phase SAA response. These results suggest that colchicine inhibits amyloidosis in the predeposition phase, possibly by blocking formation of amyloid-enhancing factor.
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000188:drug therapy*; D000818:Animals; D003078:Colchicine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage; D006133:Growth Substances / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012835:Silver Nitrate; D013154:Spleen / Q000032:analysis
D000682:Amyloid; D006023:Glycoproteins; D006133:Growth Substances; D000685:Serum Amyloid A Protein; C046748:amyloid enhancing factor; D012835:Silver Nitrate; D003078:Colchicine