MONOCYTE ANERGY IN SEPTIC SHOCK IS ASSOCIATED WITH A PREDILECTION TO APOPTOSIS AND IS REVERSED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATINGFACTOR EX-VIVO

The effects of priming monocytes from septic patients with granulocyte -macrophage colony-stimulating factor (GM-CSF) ex vivo were investigat ed. Monocytes from septic patients had depressed plasma GM-CSF and dys regulated levels of other cytokines compared with normal subjects. Mem brane expression of CD71 and HLA-DR were depressed, and monocytes were anergic to lipopolysaccharide (LPS) stimulation in vitro, which was a ssociated with spontaneous and accelerated activation-induced apoptosi s by LPS. Priming monocytes with GM-CSF ex vivo augmented membrane cyt okine expression, CD71, and HLA-DR. GPI I-CSF priming augmented cytoki ne secretion in response to LPS stimulation, restored cytokine secreti on in monocytes from septic patients, and reversed their predilection to undergo apoptosis, Thus, monocyte dysfunction in septic shock is as sociated with depressed plasma levels of GM-CSF and enhanced apoptosis ; however, GM-CSF stimulation ex vivo restored normal monocyte functio n and cytokine secretion by a mechanism that may depend on abrogating apoptosis.