Monocyte deactivation in neutropenic acute respiratory distress syndrome patients treated with granulocyte colony-stimulating factor.
BACKGROUND
In severely neutropenic septic acute respiratory distress syndrome (ARDS) patients, macrophages and monocytes are the last potentially remaining innate immune cells. We have previously shown, however, a deactivation of the alveolar macrophage in neutropenic septic ARDS patients. In the present study, we tried to characterize in vitro monocyte baseline cytokine production and responsiveness to lipopolysaccharide exposure.


METHODS
Twenty-two consecutive patients with cancer were prospectively enrolled into a prospective observational study in an intensive care unit. All patients developed septic ARDS and were divided into two groups: neutropenic patients (n = 12) and non-neutropenic patients (n = 10). All of the neutropenic patients received granulocyte colony-stimulating factor whereas no patient in the non-neutropenic group received granulocyte colony-stimulating factor. We compared monocytes from neutropenic patients with septic ARDS with monocytes from non-neutropenic patients and healthy control individuals (n = 10). Peripheral blood monocytes were cultured, and cytokine levels (TNFalpha, IL-1beta, IL-6, IL-10, and IL-1 receptor antagonist) were assayed with and without lipopolysaccharide stimulation.


RESULTS
TNFalpha, IL-6, IL-10 and IL-1 receptor antagonist levels in unstimulated monocytes were lower in neutropenic patients compared with non-neutropenic patients. Values obtained in the healthy individuals were low as expected, comparable with neutropenic patients. In lipopolysaccharide-stimulated monocytes, both inflammatory and anti-inflammatory cytokine production were significantly lower in neutropenic patients compared with non-neutropenic patients and control individuals.


CONCLUSIONS
Consistent with previous results concerning alveolar macrophage deactivation, we observed a systemic deactivation of monocytes in septic neutropenic ARDS. This deactivation participates in the overall immunodeficiency and could be linked to sepsis, chemotherapy and/or the use of granulocyte colony-stimulating factor.
Mokart
Djamel
D
Department of Anesthesiology and Intensive Care Unit, Paoli-Calmette Institute, 232 bd Sainte Marguerite, 13273 Marseille Cedex 9, France. mokartd@marseille.fnclcc.fr
Kipnis
Eric
E
Guerre-Berthelot
Pierre
P
Vey
Norbert
N
Capo
Christian
C
Sannini
Antoine
A
Brun
Jean-Paul
JP
Blache
Jean-Louis
JL
Mege
Jean-Louis
JL
Blaise
Didier
D
Guery
Benoit P
BP
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009369:Neoplasms / Q000150:complications; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D016179:Granulocyte Colony-Stimulating Factor