Protective effects of a novel 32-amino acid C-terminal fragment of CAP18 in endotoxemic pigs.
BACKGROUND
Cationic antimicrobial protein of 18 kd (CAP18) is a neutrophil-derived peptide that binds lipopolysaccharide (LPS) with high affinity. We hypothesized that CAP18(106-137), a novel synthetic 32-amino acid C-terminal fragment of CAP18, would neutralize the physiologic derangements induced by LPS in anesthetized swine.


METHODS
Pigs were randomly allocated into three groups. Those in the LPS group (n = 6) were infused with LPS (3 micrograms/kg/hr for 4 hours). Pigs in the LPS/CAP18 group (n = 6) were challenged with LPS (3 micrograms/kg/hr for 4 hours) and also treated with CAP18(106-137) (4 mg/kg/hr for 4 hours). Pigs in the RL group (n = 4) received neither LPS nor CAP18(106-137).


RESULTS
Treatment with CAP18(106-137) blocked LPS-induced increases in plasma levels of 6-keto-prostaglandin F1 alpha and tumor necrosis factor-alpha and prevented LPS-induced changes in cardiac output, arterial PO2, phagocyte activation, and peripheral leukocyte count. Changes in circulating concentrations of thromboxane B2, mean pulmonary artery pressure, and dynamic pulmonary compliance were attenuated in the LPS/CAP18 group.


CONCLUSIONS
Treatment with CAP18(106-137) neutralizes many of the deleterious effects of LPS in pigs.
VanderMeer
T J
TJ
Department of Surgery, Beth Israel Hospital, Boston, MA 02215, USA.
Menconi
M J
MJ
Zhuang
J
J
Wang
H
H
Murtaugh
R
R
Bouza
C
C
Stevens
P
P
Fink
M P
MP
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D054804:Cathelicidins; D004195:Disease Models, Animal; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000097:blood; D004926:Escherichia coli; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000097:blood; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009895:Opsonin Proteins / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D004731:Endotoxins; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010100:Oxygen