title: Effect of granulocyte-monocyte colony-stimulating factor therapy on leukocyte function and clearance of serious infection in nonneutropenic patients.
abstract: OBJECTIVE
  Impaired leukocyte function in patients with serious infections may increase mortality. Granulocyte-monocyte colony-stimulating factor (GM-CSF) broadly activates peripheral monocytes and neutrophils. We performed a clinical trial of GM-CSF in septic, hemodynamically stable patients to see whether GM-CSF treatment improved leukocyte function and mortality.
  
  
  METHODS
  Randomized, unblinded, placebo-controlled, prospective study.
  
  
  METHODS
  A 600-bed academic tertiary care center with a 120-bed ICU census with a high proportion of immunocompromised, solid-organ transplant recipients.
  
  
  METHODS
  Forty adult patients with infections meeting the criteria for the systemic inflammatory response syndrome but without hemodynamic instability or shock.
  
  
  METHODS
  Patients with sepsis and a documented infection were randomized to a 72-h infusion of GM-CSF (125 microg/m2) or placebo.
  
  
  RESULTS
  GM-CSF infusion caused the up-regulation of the beta2-integrin adhesion molecule CD11b and the appearance of the activated ("sticky" or "avid") form of the molecule on circulating neutrophils and monocytes. CD11b density and avidity increases in response to the administration of tumor necrosis factor-alpha were blunted prior to treatment in these patients with serious infection. GM-CSF partially repaired this blunted response on both monocytes and neutrophils. It also caused the down-regulation of the adhesion molecule L-selectin on neutrophils and the up-regulation of human leukocyte antigen on monocytes. These changes were consistent with a broad activation of the circulating leukocyte pool. Although mortality and organ failure scores were similar in both groups, infection resolved significantly more often in patients receiving GM-CSF.
  
  
  CONCLUSIONS
  GM-CSF infusion up-regulated the functional markers of inflammation on circulating neutrophils and monocytes and was associated with both the clinical and microbiological resolution of infection. There was no detectable exacerbation of sepsis-related organ failure or other deleterious side effects with the administration of this proinflammatory agent to patients with serious infections.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh Medical Center, 642 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261. ajr3@pitt.edu
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Rosenbloom
authors.forename: Peter K
authors.initials: PK
authors.lastname: Linden
authors.forename: Adrienne
authors.initials: A
authors.lastname: Dorrance
authors.forename: Nicole
authors.initials: N
authors.lastname: Penkosky
authors.forename: Mark H
authors.initials: MH
authors.lastname: Cohen-Melamed
authors.forename: Michael R
authors.initials: MR
authors.lastname: Pinsky
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor