Monocyte deactivation in neutropenic acute respiratory distress syndrome patients treated with granulocyte colony-stimulating factor

INTRODUCTION 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. CONCLUSION 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.