• Melvyn Lynn, Daniel P Rossignol, Janice L Wheeler, Richard J Kao, Carlos A Perdomo, Robert Noveck, Ramon Vargas, Tony D'Angelo, Sandra Gotzkowsky, and F Gilbert McMahon.
• Eisai Medical Research, Teaneck, New Jersey 07666-6741, USA. melvyn_lynn@eisai.com
• J. Infect. Dis. 2003 Feb 15; 187 (4): 631-9.

AbstractE5564 is a second-generation synthetic analogue of the lipid A component of endotoxin (lipopolysaccharide [LPS]). The ability of E5564 to block the toxic activity of LPS was assessed in a double-blind, placebo-controlled study. A bolus infusion of endotoxin (4 ng/kg) was administered to healthy subjects to induce a mild transient syndrome similar to clinical sepsis. Single E5564 doses of 50-250 microg ameliorated or blocked all of the effects of LPS in a dose-dependent manner. All E5564 dose groups had statistically significant reductions in elevated temperature, heart rate, C-reactive protein levels, white blood cell count, and cytokine levels (tumor necrosis factor-alpha and interleukin-6), compared with placebo (P<.01). In doses of > or = 100 microg, E5564 acted as an LPS antagonist and completely eliminated these signs. E5564 also blocked or ameliorated LPS-induced fever, chills, headache, myalgia, and tachycardia (P<.01). These results demonstrate that E5564 blocks the effects of LPS in a human model of clinical sepsis and indicate its potential in the treatment and/or prevention of clinical sepsis.

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