PMID- 7630120
OWN - NLM
STAT- MEDLINE
DCOM- 19950905
LR  - 20190817
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 59
IP  - 1
DP  - 1995 Jul
TI  - PEG-BP-30 monotherapy attenuates the cytokine-mediated inflammatory cascade in 
      baboon Escherichia coli septic shock.
PG  - 153-8
AB  - 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-alpha (TNF alpha) is known to 
      contribute to hemodynamic collapse and the hematological dyscrasia associated 
      with gram-negative sepsis. Although previous studies have shown TNF alpha 
      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 non-human 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 10(10) 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 (TNF alpha, IL-1 beta, 
      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.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Espat, N J
AU  - Espat NJ
AD  - Department of Surgery, University of Florida College of Medicine, Gainesville.
FAU - Cendan, J C
AU  - Cendan JC
FAU - Beierle, E A
AU  - Beierle EA
FAU - Auffenberg, T A
AU  - Auffenberg TA
FAU - Rosenberg, J
AU  - Rosenberg J
FAU - Russell, D
AU  - Russell D
FAU - Kenney, J S
AU  - Kenney JS
FAU - Fischer, E
AU  - Fischer E
FAU - Montegut, W
AU  - Montegut W
FAU - Lowry, S F
AU  - Lowry SF
AU  - et al.
LA  - eng
GR  - CA-50281/CA/NCI NIH HHS/United States
GR  - GM-40586/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Cytokines)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Animals
MH  - Cytokines/*physiology
MH  - Escherichia coli Infections/blood/*drug therapy/physiopathology
MH  - Female
MH  - Hemodynamics/drug effects
MH  - Inflammation/*drug therapy
MH  - Interleukins/blood
MH  - Male
MH  - Papio
MH  - Polyethylene Glycols/therapeutic use
MH  - Receptors, Tumor Necrosis Factor/*physiology
MH  - Recombinant Proteins/therapeutic use
MH  - Shock, Septic/blood/*drug therapy/physiopathology
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 1995/07/01 00:00
MHDA- 1995/07/01 00:01
CRDT- 1995/07/01 00:00
PHST- 1995/07/01 00:00 [pubmed]
PHST- 1995/07/01 00:01 [medline]
PHST- 1995/07/01 00:00 [entrez]
AID - S002248048571147X [pii]
AID - 10.1006/jsre.1995.1147 [doi]
PST - ppublish
SO  - J Surg Res. 1995 Jul;59(1):153-8. doi: 10.1006/jsre.1995.1147.