A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoiesis and effector functions of granulocytes and macrophages and is involved in pulmonary surfactant homeostasis. We investigated whether GM-CSF therapy improved clinically diagnosed severe sepsis and respiratory dysfunction in critically ill patients. This randomized, double-blind, placebo-controlled phase II study added low-dose (3 mcg/kg) intravenous recombinant human GM-CSF daily for 5 days to conventional therapy in 10 patients, with a further eight patients receiving placebo. GM-CSF-treated patients showed improvement in Pa(O(2))/FI(O(2)) over 5 days (p = 0.02) and increased peripheral blood neutrophils (p = 0.08), whereas alveolar neutrophils decreased (p = 0.02). GM-CSF therapy was not associated with decreased 30-day survival or with increased acute respiratory distress syndrome or extrapulmonary organ dysfunction. GM-CSF therapy was associated with increased blood granulocyte superoxide production and restoration or preservation of blood and alveolar leukocyte phagocytic function. We conclude that low-dose GM-CSF was associated with improved gas exchange without pulmonary neutrophil infiltration, despite functional activation of both circulating neutrophils and pulmonary phagocytes. In addition, GM-CSF therapy was not associated with worsened acute respiratory distress syndrome or the multiple organ dysfunction syndrome, suggesting a homeostatic role for GM-CSF in sepsis-related pulmonary dysfunction.
Intensive Care Unit, The Royal Melbourne Hospital, Victoria, Australia. intensive@ozemail.com.au
Jeffrey J
JJ
Presneill
Trudi
T
Harris
Alastair G
AG
Stewart
John F
JF
Cade
John W
JW
Wilson
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011659:Pulmonary Gas Exchange; D011994:Recombinant Proteins; D012120:Respiration Disorders / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications* / Q000276:immunology
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor