A Randomized Phase II Trial of Granulocyte-Macrophage Colony-Stimulating Factor Therapy in Severe Sepsis with Respiratory Dysfunction

• Published in: American journal of respiratory and critical care medicine Vol. 166; no. 2; pp. 138 - 143
• Main Authors: Presneill, Jeffrey J, Harris, Trudi, Stewart, Alastair G, Cade, John F, Wilson, John W
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.07.2002; American Lung Association
• Subjects: Adult; Aged; Biological and medical sciences; Double-Blind Method; Female; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - adverse effects; Humans; Infusions, Intravenous; Leukocytes - immunology; Male; Medical sciences; Middle Aged; Neutrophils - immunology; Phagocytosis; Pharmacology. Drug treatments; Pulmonary Gas Exchange; Recombinant Proteins; Respiration Disorders - complications; Respiration Disorders - physiopathology; Respiration Disorders - therapy; Respiratory Distress Syndrome, Adult - complications; Respiratory Distress Syndrome, Adult - physiopathology; Respiratory Distress Syndrome, Adult - therapy; Respiratory system; Systemic Inflammatory Response Syndrome - complications; Systemic Inflammatory Response Syndrome - immunology; Human; Pathophysiology; Respiratory disease; Leukocyte; Critically ill; Treatment efficiency; Exploration; Infection; Sepsis syndrome; Chemotherapy; Lung function; Treatment; Phase II trial; Complication; Mechanism of action; Granulocyte macrophage colony stimulating factor
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.2009005

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.