Lovastatin inhibits formation of AA amyloid.

Amyloid A (AA) amyloidosis is a severe complication of many chronic inflammatory disorders, including the hereditary periodic fever syndromes. However, in one of these periodic fever syndromes, the hyper IgD and periodic fever syndrome, amyloidosis is rare despite vigorous, recurring inflammation. This he- reditary syndrome is caused by mutations in the gene coding for mevalonate kinase, an enzyme of the isopre- noid pathway. In this study, we used a cell culture sys- tem with human monocytes to show that inhibition of the isoprenoid pathway inhibits amyloidogenesis. Inhi- bition of the isoprenoid pathway by lovastatin resulted in a dose-dependent reduction of amyloid formed (53% at 10 M( P0.01)) compared with mononuclear cells that are exposed only to serum AA. The inhibitory effects of lovastatin are reversible by addition of farne- sol but not geranylgeraniol. Farnesyl transferase inhibi- tion also inhibited amyloidogenesis. These results impli- cate that the isoprenoid metabolism could be a potential target for prevention and treatment of AA amyloidosis. J. Leukoc. Biol. 83: 1295-1299; 2008.