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Effects of bactericidal/permeability-increasing protein on endotoxin-induced fever and Escherichia coli-induced shock in rabbits

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

H.N. Paddock

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

F. Cominelli

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

M.N. Marra

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

R.W. Scott

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

S.D. Schwaitzberg

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

C.A. Dinarello

Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Department of Surgery, Tufts University and New England Medical Center Hospital, Boston, MA, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, Incyte Pharmaceuticals Inc., Palo Alto, CA, USA

Binding of bactericidal/permeability-increasing protein (BPI) to endotoxin inhibits endotoxin-triggered responses. We investigated the effects of BPI on endotoxin fever and E. coli-induced septic shock in rabbits. Pre-incubation of endotoxin with BPI blocked fever compared to control rabbits (n = 6). A marked reduction in fever was also observed when BPI was injected before endotoxin. E. coli-challenge resulted in 66% mortality (n = 6); pre-treatment with BPI resulted in survival of all animals (n = 3). Mean arterial blood pressure was higher in BPI-treated compared to control rabbits. Comparable leukopenia and thrombocytopenia was observed with either BPI or vehicle treatment. Tumor necrosis factor (TNF) and interleukin-1 receptor antagonist were similarly elevated in both BPI- and saline-treated rabbits. However, in BPI treated rabbits, peak TNF levels were 34 % lower compared to saline controls (P < 0.05). Further studies are warranted to assess whether BPI may have therapeutic potential for the treatment of septic shock.

Journal of Endotoxin Research, Vol. 2, No. 1, 9-18 (1995)
DOI: 10.1177/096805199500200102


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