Mepacrine-Induced Sensitization of Rats to Bacterial Endotoxin
NAVAL MEDICAL RESEARCH INST BETHESDA MD
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Investigations in the past several years have implicated prostaglandin release in the pathogenesis of endotoxin shock. These studies have focused on the observation that prostaglandin levels are increased following endotoxin administration. Furthermore, indomethacin, a compound that inhibits prostaglandin formation, has been shown to protect animals from bacterial endotoxin. Since another affect of indomethacin is to inhibit phospholipase A2, the initial purpose of this study was to determine whether or not other inhibitors of phospholipase A2, such as mepacrine, would also be protective. Information of this nature would be useful in understanding the mechanism of endotoxin toxicity, as well as a possible treatment for sepsis. Thus, we injected rats with endotoxin and mepacrine. Instead of protection, however, we found that mepacrine sensitized the animals to endotoxin.
- Medicine and Medical Research