Perioperative recombinant human granulocyte colony-stimulating factor (Filgrastim) treatment prevents immunoinflammatory dysfunction associated with major surgery

Abstract

Objective: To examine the effects of perioperative rhG-CSF administration on immune function in patients subjected to major surgery.

Summary background data: Severe trauma, such as major surgery, initiates acute immunodysfunction which predisposes the patient towards infectious complications.

Methods: Sixty patients undergoing elective surgery received either recombinant human granulocyte colony-stimulating factor/rh G-CSF (Filgrastim) or a placebo perioperatively. At several time points before and after the surgical intervention immunofunctional parameters were assessed. RESULTS Leukocyte counts and serum levels of anti-inflammatory mediators (IL-1ra and TNF-R) were increased in Filgrastim-treated patients, while the post-operative acute phase response was attenuated. Monocyte deactivation (reduced TNF-alpha release and HLA-DR expression) and lymphocyte anergy (impaired mitogenic proliferation and reduced TH1 lymphokine release) were blunted and the incidence and severity of infectious complications were reduced.

Conclusions: These results suggest that Filgrastim treatment reinforces innate immunity, enabling better prevention of infection. Thus, this unique combination of hematopoietic, anti-inflammatory and anti-infectious effects on the innate immune system warrants further study of clinical efficacy and sepsis prophylaxis.

FIGURE 1. The experimental protocol of the study is depicted. Patients in the treatment group received rh G-CSF (15 μg/kg body weight) over 6 perioperative days either as 3 bolus administrations of 5 μg/kg body weight or as a continuous administration of 2 μg/kg body weight following an initial bolus of 5 μg/kg body weight.

FIGURE 2. Perioperative Filgrastim treatment blunts trauma-induced acute phase reaction. Patients received placebo (empty bars) or Filgrastim (black bars) perioperatively. Total leukocyte counts (a), C-reactive protein (b) and G-CSF (c) serum concentrations are shown as means ± SEM *P ≤ 0.05; **P ≤ 0.001, relative to placebo values.

FIGURE 3. Perioperative Filgrastim treatment blunts trauma-induced monocyte deactivation. Patients received placebo (empty bars) or Filgrastim (black bars) perioperatively. a: HLA-DR expression on monocytes. LPS-induced TNF-α (b), IL-6 (c), and IL-1ra (d) release in diluted whole blood. Data represent means ± SEM. *P ≤ 0.05; **P ≤ 0.001, relative to placebo values.