LEUKOCYTE CD18 MONOCLONAL-ANTIBODY WORSENS ENDOTOXEMIA AND CARDIOVASCULAR INJURY IN CANINES WITH SEPTIC SHOCK

We investigated the effects of a murine monoclonal antibody directed a gainst 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 b efore clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 do ses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, mur ine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxone, 100 mg.kg-1.day-1 for 4 days). Two o f 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 l evels and higher (P < 0.05) neutrophil counts. Day 1 after clot placem ent, MAb animals, compared with control animals, had decreased (P < 0. 05) central venous pressure and arterial pH and increased (P < 0.05) a rterial lactate. Day 2 after clot placement, MAb animals, compared wit h control animals, had decreased (P < 0.05) cardiac index and mean art erial pressure. In summary, MAb R15.7, although associated with increa sed neutrophil counts, worsened serum endotoxemia, acidosis, and cardi ovascular function in this canine model of septic shock. These data su ggest that in septic shock, antibody directed against this leukocyte m embrane protein complex may be harmful, possibly via impairment of nor mal leukocyte function.