+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI



Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI



Annals of Surgery 220(1): 77-85



The in vivo neutralizing activities of an anti-lipopolysaccharide (LPS) antibody HA-1A (Centoxin [Centocor, Malvern, PA]), a human immunoglobulin M monoclonal antibody, and of bactericidal/permeability-increasing protein (BPI), an endogenously produced human LPS-neutralizing protein, were studied in a primate model of lethal Escherichia coli bacteremia. HA-1A has been used with variable success against LPS activity in some animal models and in a recently reported clinical trial. However, no data assessing the efficacy of this agent in subhuman primates is available. Bactericidal/permeability-increasing protein is a product of polymorphomononuclear cells (PMNs) that is stored in azurophilic granules and exhibits LPS-neutralizing activity in vitro and in some in vivo models. Immediately after E. coli infusion and in a blinded fashion, three baboons were treated with BPI (5 mg/kg bolus infusion and 95 micrograms/kg/min infusion over 4 hr). Three animals received 3 mg/kg BW of HA-1A, whereas another three baboons received a placebo treatment. The BPI-treated animals demonstrated significantly (p < 0.03) lower circulating LPS-limulus amoebocyte lysate (LAL) activity compared with the control animals, but this reduction in LPS-LAL activity was not associated with improved survival. HA-1A treatment did not reduce LPS-LAL activity. However, both BPI and HA-1A treatment did attenuate the pro-inflammatory cytokine response. The current data suggests that incomplete neutralization of endotoxin activity does not alter mortality from severe bacteremia. Given the diversity of mediator production under such circumstances, a strategy of combination therapy in the form of anti-lipopolysaccharide and anticytokine treatment may be necessary to achieve optimal survival.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 045269300

Download citation: RISBibTeXText

PMID: 8024362

DOI: 10.1097/00000658-199407000-00011


Related references

Impact of anti-endotoxin therapy utilizing bactericidal-permeability-increasing protein during primate bacteremia. Surgical Forum 44: 111-114, 1993

Protective effect of anti-endotoxin therapy and nitric oxide synthase blockade in rat bacteremia. FASEB Journal 9(4): A889, 1995

Monoclonal anti-endotoxin antibodies for the treatment of gram-negative bacteremia and septic shock. European Journal of Clinical Microbiology and Infectious Diseases 9(10): 711-716, 1990

Endotoxin activity level and septic shock: a possible role for specific anti-endotoxin therapy?. Contributions to Nephrology 167: 102-110, 2010

Recombinant proteins and peptides for endotoxin biosensors, endotoxin removal, and anti-microbial and anti-endotoxin therapeutics. Official Gazette of the United States Patent & Trademark Office Patents 1281(2), 2004

Anti endotoxin therapy effect on survival immune function and serum endotoxin levels in a burn sepsis model. FASEB Journal 3(3): A917, 1989

Mortality rate and bacteremia, endotoxin, and endothelin-1 levels in antibiotic therapy for E. coli septic peritonitis. Apmis 101(2): 97, 1993

Endotoxin concentration in neutropenic patients with suspected gram-negative sepsis: correlation with clinical outcome and determination of anti-endotoxin core antibodies during therapy with polyclonal immunoglobulin M-enriched immunoglobulins. Antimicrobial Agents and ChemoTherapy 36(10): 2139-2146, 1992

Bactericidal permeability increasing protein as an anti endotoxin therapeutic agent comparisons with anti core glycolipid polyclonal antibody therapy. Clinical Research 40(2): 213A, 1992

Anti-endotoxin therapy and the management of sepsis. Journal of Antimicrobial ChemoTherapy 29(4): 360-363, 1992

Anti-endotoxin therapy in liver diseases. Giornale Italiano di Chemioterapia 26(1-2): 241-256, 1979

Economic benefit of anti-endotoxin therapy in veterinary practice. Journal of the South African Veterinary Association 57(1): 73-73, 1986

Changes of circulating Lps and cytokines in burned patients after anti-endotoxin therapy. Zhonghua Yi Xue Za Zhi 76(5): 355-358, 1996

Projected impact of monoclonal anti-endotoxin antibody therapy. Archives of Internal Medicine 154(11): 1241-1249, 1994

Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha as acne inversa therapy. Journal of Clinical Microbiology 50(3): 1109-1112, 2012