PEG-BP-30 monotherapy attenuates the cytokine-mediated inflammatory cascade in baboon Escherichia coli septic shock

Academic Article


  • Septic shock following gram-negative infection is a leading cause of mortality in critically ill patients, accounting for nearly 200,000 deaths a year. The exaggerated production of tumor necrosis factor-α (TNFα) is known to contribute to hemodynamic collapse and the hematological dyserasia associated with gram-negative sepsis. Although previous studios have shown TNFα antibodies and TNF immunoadhesins to be effective in experimental gram- negative sepsis, we postulated that administration of a novel construct of two modified soluble p55 receptors linked to polyethylene glycol (PEG-BP-30) would also attenuate the hemodynamic and hematologic alterations to lethal Escherichia coli septic shock in nonhuman primates. Nine adult female and male baboons (Papio anubis), weighing 10-17 kg, were anesthetized and invasively monitored. The nine animals were randomized to receive either 0.2 mg/kg body wt PEG-BP-30 (n = 3), 5.0 mg/kg body wt PEG-BP-30 (n = 3), or placebo (n = 3). One hour after pretreatment, animals were infused with 5-10 x 1020 CFU/kg of live E. coli iv and vital signs were recorded for the next 8 hr. Arterial blood was drawn for baseline parameters and throughout the study to obtain total and differential white blood cell and platelet counts and cytokine levels (TNFα, IL-1β, IL-6, IL-8). E. coli bacteremic baboons receiving only placebo demonstrated a significant fall in mean blood pressure and leukopenia. Two of the three animals expired. In contrast, five of the six baboons receiving the PEG-BP-30 survived and these animals exhibited markedly attenuated declines in blood pressure and leukocyte numbers. Septic baboons also manifested monophasic plasma TNFα, IL-1β, IL-6, and IL-8 responses that were significantly attenuated by PEG-BP-30 pretreatment in a dose-dependent manner. We conclude from these data that the administration of PEG-BP-30 improves survival and attenuates the TNFα-mediated pathophysiology in E. coli sepsis. © 1995 Academic Press, Inc.
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    Author List

  • Espat NJ; Cendan JC; Beierle EA; Auffenberg TA; Rosenberg J; Russell D; Kenney JS; Fischer E; Montegut W; Lowry SF
  • Start Page

  • 153
  • End Page

  • 158
  • Volume

  • 59
  • Issue

  • 1