title: Transient inhibition of neutrophil adherence with the anti-CD18 monoclonal antibody 60.3 does not increase mortality rates in abdominal sepsis.
abstract: Monoclonal antibodies (MAbs) that recognize the neutrophil (PMN) adherence complex CD11/CD18 inhibit PMN adherence to endothelium and attenuate PMN-mediated ischemia-reperfusion injury. One consideration regarding the clinical usefulness of such therapy is whether transient inhibition of PMN adherence or function will impede host defense and increase susceptibility to infection and sepsis. We studied susceptibility to sepsis in New Zealand white rabbits with an appendiceal devascularization model to answer the question: Does inhibition of PMN adherence with the anti-CD18 MAb 60.3 increase morbidity and mortality rates in abdominal sepsis? Four treatment groups of 10 animals each were studied: group 1 (controls) received no treatment, group 2 received MAb 60.3, group 3 was given the antibiotic cefazolin alone, and group 4 received both cefazolin and MAb 60.3. PMN emigration into the peritoneum was inhibited significantly in MAb 60.3-treated animals (groups 2 and 4). There was no difference in weight loss, incidence of infectious complications, or mortality rates when MAb 60.3-treated animals were compared with untreated animals. These results demonstrate that transient inhibition of PMN adherence does not increase morbidity or mortality rates in this model of abdominal sepsis. These results suggest that if MAb 60.3 or similar antibodies are used to prevent PMN-mediated injury, they will not increase susceptibility to sepsis.
authors.affiliation: Department of Surgery, University of Washington School of Medicine, Seattle.
authors.forename: W J
authors.initials: WJ
authors.lastname: Mileski
authors.forename: R K
authors.initials: RK
authors.lastname: Winn
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
authors.forename: C L
authors.initials: CL
authors.lastname: Rice
mesh_terms: D000005:Abdomen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000166:cytology / Q000382:microbiology; D001424:Bacterial Infections / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D002437:Cefazolin / Q000627:therapeutic use; D002448:Cell Adhesion / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D015996:Survival Rate; D015431:Weight Loss
chemical_list: D000911:Antibodies, Monoclonal; D002437:Cefazolin