Reduced interferon-gamma release in patients recovered from Legionnaires' disease.

Abstract

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. 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. 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). These results suggest that impaired IFN-gamma production may contribute to susceptibility to L pneumophila infection.