Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator

Porphyromanas gingivalis strain 381 lipid A showed lower activity in induci ng interreukin (IL)-1 alpha and IL-1 beta production and cytokine mRNA expr ession than synthetic Escherichia coil lipid A (compound 506) in alveolar m acrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor alpha in alveolar macrophages and IL-6 in peritoneal macrophages. A calmod ulin (CaM) antagonist, W-7, inhibited IL-I beta production and its mRNA exp ression induced by P. gingivalis lipid A but not compound 506 in alveolar m acrophages. A CaM kinase activator reduced the induction of IL-1 beta in th e serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxi c sepsis. (C) 2000 Federation of European Microbiological Societies. Publis hed by Elsevier Science B.V. All rights reserved.