Abstract
Excessive synthesis and release of proinflammatory cytokines during endotoxemia causes severe pathophysiological derangements and organ failure. Because the lysosomotropic agent chloroquine has been effective in the treatment of diseases associated with increased secretion of proinflammatory cytokines such as malaria or rheumatoid arthritis, this study evaluates the potential effect of chloroquine on endotoxin-induced cytokinemia using human whole blood from healthy volunteers. Chloroquine revealed a dose-dependent inhibitory effect on endotoxin-induced secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 that was associated with reduced cytokine mRNA expression. Moreover, ammonia and methylamine, which react as weak bases like chloroquine, reduced synthesis and secretion of proinflammatory cytokines. These data indicate a potent anti-inflammatory effect of chloroquine on endotoxin-induced synthesis of proinflammatory cytokines that may be due to its weak base effect. Thus chloroquine may be of therapeutic benefit not only, during chronic inflammation but also in diseases that are related to bacteria-induced inflammation.
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