title: Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock.
abstract: We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock. Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot. Starting 12 h before clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days). Two of eight control animals and four of eight MAb animals died (P = 0.4). During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts. Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate. Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure. In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock. These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function.
authors.affiliation: Critical Care Medicine Department, National Institutes of Health, Bethesda 20892.
authors.forename: P Q
authors.initials: PQ
authors.lastname: Eichacker
authors.forename: W D
authors.initials: WD
authors.lastname: Hoffman
authors.forename: A
authors.initials: A
authors.lastname: Farese
authors.forename: R L
authors.initials: RL
authors.lastname: Danner
authors.forename: A F
authors.initials: AF
authors.lastname: Suffredini
authors.forename: Y
authors.initials: Y
authors.lastname: Waisman
authors.forename: S M
authors.initials: SM
authors.lastname: Banks
authors.forename: T
authors.initials: T
authors.lastname: Mouginis
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Rothlein
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D002319:Cardiovascular System / Q000276:immunology / Q000293:injuries*; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity; D007958:Leukocyte Count; D009504:Neutrophils; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D012772:Shock, Septic / Q000097:blood / Q000150:complications / Q000276:immunology*; D014115:Toxemia / Q000097:blood / Q000150:complications / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D004731:Endotoxins; D016028:Receptors, Leukocyte-Adhesion