Reduced interferon-gamma release in patients recovered from Legionnaires' disease.
BACKGROUND
Legionella pneumophila, a Gram negative intracellular pathogen, causes Legionnaires' disease (LD). Interferon (IFN)-gamma is important for host defence against L pneumophila so reduced IFN-gamma 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-gamma production, and with IFN-gamma to evaluate IFN-gamma 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-gamma 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-gamma responsiveness, measured by release of IFN-gamma inducible protein (IP)-10, tumour necrosis factor alpha, IL-12 production capacity, and monocyte expression of complement receptor 3, did not differ between patients and controls. IFN-gamma release after stimulation with LPS and IP-10 release after stimulation with IFN-gamma were weakly associated with severity of LD in the former patient group (rho=-0.3, p=0.011 and rho=-0.3, p=0.037, respectively).


CONCLUSIONS
These results suggest that impaired IFN-gamma production may contribute to susceptibility to L pneumophila infection.
Lettinga
K D
KD
Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. k.d.Lettinga@amc.uva.nl
Weijer
S
S
Speelman
P
P
Prins
J M
JM
Van Der Poll
T
T
Verbon
A
A
D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007877:Legionnaires' Disease / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism
D007378:Interleukins; D016177:Macrophage-1 Antigen; D007371:Interferon-gamma