Monocyte anergy in septic shock is associated with a predilection to apoptosis and is reversed by granulocyte-macrophage colony-stimulating factor ex vivo.
The effects of priming monocytes from septic patients with granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo were investigated. Monocytes from septic patients had depressed plasma GM-CSF and dysregulated levels of other cytokines compared with normal subjects. Membrane expression of CD71 and HLA-DR were depressed, and monocytes were anergic to lipopolysaccharide (LPS) stimulation in vitro, which was associated with spontaneous and accelerated activation-induced apoptosis by LPS. Priming monocytes with GM-CSF ex vivo augmented membrane cytokine expression, CD71, and HLA-DR. GM-CSF priming augmented cytokine secretion in response to LPS stimulation, restored cytokine secretion in monocytes from septic patients, and reversed their predilection to undergo apoptosis. Thus, monocyte dysfunction in septic shock is associated with depressed plasma levels of GM-CSF and enhanced apoptosis; however, GM-CSF stimulation ex vivo restored normal monocyte function and cytokine secretion by a mechanism that may depend on abrogating apoptosis.
Department of Haematology, St. Bartholomew's and Royal London School of Medicine and Dentistry, London, United Kingdom. m.williams@mds.qmw.ac.uk
M A
MA
Williams
S
S
Withington
A C
AC
Newland
S M
SM
Kelsey
D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin; D012772:Shock, Septic / Q000276:immunology* / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D016207:Cytokines; D006684:HLA-DR Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011990:Receptors, Transferrin; D051028:bcl-2-Associated X Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor