Antibiotic therapy determines subcutaneous Escherichia coli abscess formation after CD18 inhibition in rabbits.
Monoclonal antibodies (MAbs) that interrupt polymorphonuclear neutrophil (PMN)-endothelial cell adhesion can ameliorate PMN-mediated injury, including burn-induced inflammatory injury, but can also impair PMN-mediated defense against bacterial infection. We report the effects of combined anti-adhesion and antibiotic therapy on local infectious sequelae after subcutaneous Escherichia coli inoculation in rabbits treated with anti-CD18 (60.3) or anti-P-selectin (PB1.3) MAb. Ampicillin or ceftriaxone were administered for 72 hours. PMN emigration was assessed at 24 hours and local infectious sequelae at 7 days. In ampicillin/60.3-treated rabbits, E. coli inoculation resulted in impaired PMN emigration and increased infectious complications, with abscesses forming at a 10,000-fold lower inoculation concentration compared with other MAb-antibiotic treatment groups. We conclude that (1) CD18, but not P-selectin blockade interferes with PMN emigration and host defense to subcutaneous E. coli, and (2) appropriate antibiotic therapy can prevent the local infectious events caused by CD18 inhibition.
Department of Anesthesiology, University of Washington School of Medicine, Seattle, USA.
G A
GA
Talbott
S R
SR
Sharar
J C
JC
Paulson
J M
JM
Harlan
R K
RK
Winn
D000038:Abscess / Q000188:drug therapy* / Q000276:immunology*; D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002056:Burns / Q000150:complications; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002443:Ceftriaxone / Q000627:therapeutic use*; D002465:Cell Movement / Q000502:physiology; D002511:Cephalosporins / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D010406:Penicillins / Q000627:therapeutic use*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002511:Cephalosporins; D019007:P-Selectin; D010406:Penicillins; D002443:Ceftriaxone; D000667:Ampicillin