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Antibiotic therapy determines subcutaneous Escherichia coli abscess formation after CD18 inhibition in rabbits
G A Talbott1, S R Sharar, J C Paulson
1Department of Anesthesiology, University of Washington School of Medicine, Seattle, USA.
Abstract:
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.
Insights
Monoclonal antibodies blocking CD18 impair neutrophil defense against E. coli, increasing infection risk. However, antibiotic therapy effectively prevents these infectious complications, maintaining host defense.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Monoclonal antibodies (MAbs) targeting polymorphonuclear neutrophil (PMN)-endothelial cell adhesion can reduce inflammatory injury but may compromise bacterial defense.
- Understanding the interplay between anti-adhesion therapy and antibiotic treatment is crucial for managing infections.
Purpose of the Study:
- To investigate the impact of combined anti-adhesion MAb and antibiotic therapy on local infectious sequelae following Escherichia coli inoculation.
- To evaluate the specific roles of anti-CD18 and anti-P-selectin MAbs in modulating host defense and infectious complications.
Main Methods:
- Rabbits received subcutaneous Escherichia coli inoculation after treatment with anti-CD18 (60.3) or anti-P-selectin (PB1.3) MAbs.
- Antibiotic therapy (ampicillin or ceftriaxone) was administered for 72 hours.
- PMN emigration was assessed at 24 hours, and local infectious sequelae were evaluated at 7 days.
Main Results:
- Combined ampicillin and anti-CD18 MAb treatment resulted in impaired PMN emigration and significantly increased infectious complications (abscess formation).
- Abscesses formed at a 10,000-fold lower E. coli concentration in the ampicillin/60.3 group compared to other treatment groups.
- Anti-P-selectin MAb did not significantly impair PMN emigration or increase infectious complications.
Conclusions:
- CD18 blockade, unlike P-selectin blockade, interferes with PMN emigration and compromises host defense against subcutaneous E. coli infection.
- Appropriate antibiotic therapy is effective in preventing local infectious events that arise from CD18 inhibition.