PMID- 8195314
OWN - NLM
STAT- MEDLINE
DCOM- 19940630
LR  - 20190920
IS  - 0271-9142 (Print)
IS  - 0271-9142 (Linking)
VI  - 14
IP  - 2
DP  - 1994 Mar
TI  - The role of bactericidal/permeability-increasing protein in the treatment of 
      primate bacteremia and septic shock.
PG  - 120-33
AB  - Human neutrophil azurophilic granules contain an approximately 55-kDa protein, 
      known as bactericidal/permeability-increasing protein (BPI), which possesses a 
      high-affinity binding domain for the lipid A component of lipopolysaccharide 
      (LPS). The in vivo LPS neutralizing activity of exogenous BPI was studied in a 
      model of lethal Escherichia coli bacteremia. Five baboons were treated with BPI 
      (5 mg/kg bolus injection followed by a 95 micrograms/kg/min BPI infusion over 4 
      hr), while four additional animals received a genetically engineered variant of 
      BPI (NCY103). Five animals received a placebo treatment and served as controls. 
      Both wild-type rhBPI and NCY103 significantly (P < 0.05) decreased blood levels 
      of LPS throughout an 8-hr evaluation period following live bacterial challenge. 
      Two hours following E. coli administration, LPS levels peaked in the controls, at 
      6.86 +/- 3.22 ng/ml, whereas LPS levels were 3.39 +/- 2.1 ng/ml in the BPI group 
      and 2.04 +/- 1.18 ng/ml in the NCY103 group. Tumor necrosis factor-alpha 
      (TNF-alpha) and interleukin-6 levels likewise were attenuated in the treatment 
      groups, whereas circulating sTNFR I was significantly (P < 0.05) reduced only in 
      the BPI group. Leukocytopenia and granulocytopenia were significantly (P < 0.02) 
      lessened in the BPI group, by an average of 59% leukocytopenia and 65% 
      granulocytopenia, respectively. This study supports the concept of E. coli LPS 
      neutralization by BPI in vivo and demonstrates that a moderate (70%) reduction in 
      peak LPS-LAL activity is sufficient to alter some hematologic and cytokine 
      manifestations of bacteremia.
FAU - Rogy, M A
AU  - Rogy MA
AD  - Department of Surgery, Cornell University Medical College, New York, New York 
      10021.
FAU - Oldenburg, H S
AU  - Oldenburg HS
FAU - Calvano, S E
AU  - Calvano SE
FAU - Montegut, W J
AU  - Montegut WJ
FAU - Stackpole, S A
AU  - Stackpole SA
FAU - Van Zee, K J
AU  - Van Zee KJ
FAU - Marra, M N
AU  - Marra MN
FAU - Scott, R W
AU  - Scott RW
FAU - Seilhammer, J J
AU  - Seilhammer JJ
FAU - Moldawer, L L
AU  - Moldawer LL
AU  - et al.
LA  - eng
GR  - CA-52108/CA/NCI NIH HHS/United States
GR  - GM-34695/GM/NIGMS 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  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Blood Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bactericidal permeability increasing protein)
SB  - IM
MH  - Animals
MH  - Anti-Infective Agents/*therapeutic use
MH  - Antimicrobial Cationic Peptides
MH  - Bacteremia/*therapy
MH  - Blood Proteins/*therapeutic use
MH  - Escherichia coli Infections/*therapy
MH  - Interleukin-6/biosynthesis
MH  - *Membrane Proteins
MH  - Neutrophils/immunology
MH  - Papio
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Recombinant Proteins/therapeutic use
MH  - Shock, Septic/*therapy
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 1994/03/01 00:00
MHDA- 1994/03/01 00:01
CRDT- 1994/03/01 00:00
PHST- 1994/03/01 00:00 [pubmed]
PHST- 1994/03/01 00:01 [medline]
PHST- 1994/03/01 00:00 [entrez]
AID - 10.1007/BF01541345 [doi]
PST - ppublish
SO  - J Clin Immunol. 1994 Mar;14(2):120-33. doi: 10.1007/BF01541345.