A CD18 monoclonal antibody increases the incidence and severity of subcutaneous abscess formation after high-dose Staphylococcus aureus injection in rabbits.
Monoclonal antibody (MAb) 60.3 blocks CD18-dependent polymorphonuclear neutrophil adherence to endothelium and has been shown to be of benefit in preventing tissue injury in a variety of inflammatory conditions. However, concern exists that interference with normal polymorphonuclear neutrophil host-defense functions may increase susceptibility to bacterial infection. We compared the development of subcutaneous Staphylococcus aureus abscesses in rabbits pretreated with MAb 60.3 to those pretreated with saline placebo. Bacterial inoculation with 10(6) or 10(7) colony-forming units (CFU) did not result in abscess formation in either control or antibody-treated groups. However, inoculation with 10(8) CFU resulted in more frequent and larger abscesses in antibody-treated rabbits than in controls. Abscess incidence was similar for inoculation with 10(9) CFU, although antibody-treated rabbits developed larger abscesses than did controls. The difference in abscess development is due to delayed leukocyte migration into inoculated tissue. The results of these experiments suggest that subjects treated with MAb 60.3 and exposed to massive S. aureus inocula may be at serious risk of infection. However, despite inhibited leukocyte adhesion, inocula of up to 10(7) CFU were well tolerated in this model. Whether these findings are clinically important remains to be determined, although exposure to bacterial concentrations of 10(8) CFU or greater occurs only rarely in clinical practice.
Department of Anesthesiology, University of Washington School of Medicine, Seattle.
S R
SR
Sharar
R K
RK
Winn
C E
CE
Murry
J M
JM
Harlan
C L
CL
Rice
D000038:Abscess / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000276:immunology; D004727:Endothelium / Q000276:immunology; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D012871:Skin Diseases / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion