ROLE OF CD14 IN HEMORRHAGIC SHOCK-INDUCED ALTERATIONS OF THE MONOCYTETUMOR-NECROSIS-FACTOR RESPONSE TO ENDOTOXIN

Objective: To determine if the shock-induced alterations in whole bloo d monocyte tumor necrosis factor (TNF) response are mediated by the CD 14 receptor. Design: Prospective controlled animal experiments. Materi als and Methods: New Zealand White rabbits (n = 15) were subjected to hemorrhage and resuscitation. Blood samples obtained before shock and 24, 72, and 120 hours after shock were stimulated with lipopolysacchar ide in the presence or absence of the anti-CD14 monoclonal antibody, 6 3D3. Tumor necrosis factor was assayed using L929 cells. Measurements and Main Results: There was no detectable TNF activity in unstimulated blood. The CD14 inhibition resulted in a 55% reduction in baseline TN F activity. After shock, there,vas a marked increase in TNF activity w ith lipopolysaccharide stimulation. Addition of 63D3 resulted in a dos e-dependent 95% reduction in TNF activity at 24 and 72 hours after sho ck, (p < 0.05). Conclusion: The enhanced whole blood monocyte TNF resp onse after hemorrhage is CD14 dependent.