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Reduced interferon-γ release in patients recovered from Legionnaires' disease
  1. K D Lettinga1,
  2. S Weijer2,
  3. P Speelman1,
  4. J M Prins1,
  5. T van der Poll1,2,
  6. A Verbon1
  1. 1Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam
  1. Correspondence to:
    Dr K D Lettinga, Academic Medical Centre, Division of Infectious Diseases, Tropical Medicine and AIDS, Room F4-217, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;


Background: Legionella pneumophila, a Gram negative intracellular pathogen, causes Legionnaires' disease (LD). Interferon (IFN)-γ is important for host defence against L pneumophila so reduced IFN-γ production capacity and/or responsiveness might render humans more susceptible to infection with L pneumophila.

Methods: Seventy seven patients who suffered from LD after a point source outbreak one year earlier participated in the study. Whole blood was incubated with non-specific stimuli (lipopolysaccharide (LPS) or interleukin (IL)-12) or specific stimuli (viable or heat killed L pneumophila) to evaluate IFN-γ production, and with IFN-γ to evaluate IFN-γ responsiveness. Expression of complement receptor 3 on monocytes was determined by flow cytometry. Thirty seven companions who were also exposed but had not developed LD served as controls.

Results: Patients released less IFN-γ than controls in response to stimulation with LPS (mean (SE) 393 (58) pg/ml v 914 (178) pg/ml; p=0.001) and IL-12 (96 (14) pg/ml v 177 (41) pg/ml; p=0.058). IFN-γ responsiveness, measured by release of IFN-γ inducible protein (IP)-10, tumour necrosis factor α, IL-12 production capacity, and monocyte expression of complement receptor 3, did not differ between patients and controls. IFN-γ release after stimulation with LPS and IP-10 release after stimulation with IFN-γ were weakly associated with severity of LD in the former patient group (ρ=–0.3, p=0.011 and ρ=–0.3, p=0.037, respectively).

Conclusion: These results suggest that impaired IFN-γ production may contribute to susceptibility to L pneumophila infection.

  • Legionella pneumophila
  • interferon-γ
  • cellular immunity
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  • Financial support: Ministry of Health, the Netherlands. Grant number: CSG/PP,1074808. S Weijer is the recipient of a grant from the Netherlands Organisation of Scientific Research (NWO).

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