INHIBITION OF APOPTOSIS IN POLYMORPHONUCLEAR NEUTROPHILS FROM BURN PATIENTS

Normal human polymorphonuclear neutrophils (PMN) undergo rapid apoptos is during in vitro culture, In contrast, apoptosis is inhibited in PMN from patients with severe burns. This inhibition is not an inherent p roperty of the cells but is caused by thermolabile factors present in the plasma, Endotoxin and the proinflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alp ha) do not appear to be directly responsible, The ability of burn plas ma to inhibit apoptosis was reduced by neutralizing antibodies to huma n granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF le vels could not be detected in the burn plasma, However, the incubation of burn-derived or normal leukocyte populations consisting primarily of PMN in burn plasma induced the production of GM-C,SF, The results s uggest that activation of GM-CSF synthesis by factor(s) in burn plasma may play a role in regulating inflammation by the inhibition of apopt osis.