LEUKOCYTE CD11B/18 ANTIGEN-DIRECTED MONOCLONAL-ANTIBODY IMPROVES EARLY SURVIVAL AND DECREASES HYPOXEMIA IN DOGS CHALLENGED WITH TUMOR-NECROSIS-FACTOR

This study examined the effect of monoclonal antibody (MAb) directed against leukocyte CD11b/18 glycoprotein complex (904MAb) on cardiopulmonary injury induced by tumor necrosis factor (TNF), and death. Eighteen 2-yr-old, purpose-bred beagles with chronic tracheostomies were challenged with TNF (60-mu-g/kg of body weight) intravenously. Nine of 18 animals were treated with 0.5 to 1.0 mg/kg of body weight 904MAb intravenously 45 min before and 12, 36, and 48 h after TNF infusion. Serial femoral and pulmonary arterial catheter hemodynamics, blood gas analysis, and radionuclide cineangiographic left ventricular election fractions (EF) were done before and after a fluid challenge. Serial bronchoalveolar lavages (BAL) with cell and protein analysis also were performed using the chronic tracheostomies. Compared with animals given TNF alone, animals treated with 904MAb did not differ in overall survival (TNF alone, 219; 904MAb, 319); however, the group of animals treated with 904MAb had significantly (p < 0.01) fewer deaths within the first 30 h of TNF challenge. At 4 h after TNF challenge, all animals had significantly (p < 0.05) reduced PaO2 after fluid challenge; however, animals given 904MAb (compared with animals given TNF alone) had significantly (p < 0.05) smaller reductions in PaO2. Throughout the study, animals given 904MAb before TNF or TNF alone had similar changes in cardiac Index, mean arterial pressure, EF, and BAL protein and neutrophil concentration. Thus, MAb directed against the leukocyte CD11b/18 glycoprotein complex prolonged survival and reduced the hypoxemia occurring after TNF challenge, but this antibody did not improve overall survival or cardiopulmonary function. These results suggest that the leukocyte CD11b/18 glycoprotein complex contributes to the acute pulmonary injury and early lethality induced by TNF.