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Open Access Research article

Heparin binding protein in patients with acute respiratory failure treated with granulocyte colony-stimulating factor (filgrastim) – a prospective, placebo-controlled, double-blind study

Kirsi-Maija Kaukonen12*, Heiko Herwald3, Lennart Lindbom4 and Ville Pettila15

Author Affiliations

1 Intensive Care Unit, Helsinki University Central Hospital, Helsinki, Finland

2 ANZIC Research Centre, Department of Epidemiology and Preventative Medicine, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia

3 Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden

4 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

5 Department of Clinical Sciences, University of Helsinki, Helsinki, Finland

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BMC Infectious Diseases 2013, 13:51  doi:10.1186/1471-2334-13-51

Published: 30 January 2013

Abstract

Background

Heparin Binding Protein (HBP) is released to blood circulation from activated neutrophils in bacterial infections. It is a potential inducer of vascular leakage and precludes the development of septic shock. Filgrastim induces the production of new neutrophils and modulates their bacterial-killing activity. We evaluated the effect of filgrastim on HBP –concentrations in critically ill patients with acute respiratory failure.

Methods

59 critically ill patients with acute respiratory failure were included in this randomised, double-blind, placebo-controlled study of filgrastim 300 micrograms/day or corresponding placebo for 7 days. Plasma samples were drawn on baseline, day 4 and day 7. HBP –concentrations, absolute leukocyte and neutrophil counts were measured.

Results

The median [IQR] HBP concentrations were 23.6 ng/ml [13.9-43.0 ng/ml], 25.1 ng/ml [17.7-35.5 ng/ml] and 15.9 ng/ml [12.6-20.7 ng/ml] in patients receiving filgrastim on baseline, day 4 and day 7, respectively. The HBP concentrations in placebo group were 21.6 ng/ml [16.9-28.7 ng/ml], 13.9 ng/ml [12.0-19.5 ng/ml] and 17.8 ng/ml [13.6-20.9 ng/ml]. At day 4, the filgrastim group had significantly higher HBP –concentrations when compared to placebo group (p < 0.05). No correlation between HBP –concentrations and absolute neutrophil count or P/F –ratios was found.

Conclusions

Filgrastim treatment is associated with increased circulating HBP levels compared to placebo, but the absolute neutrophil count or the degree of oxygenation failure did not correlate with the observed plasma HBP –concentrations.

Trial registration

Clinicaltrials.gov NCT01713309

Keywords:
Filgrastim; G-CSF; Heparin-binding protein; Critically ill; Acute respiratory failure