Background: Immune defects in chronic pulmonary aspergillosis (CPA) are poorly characterized. We compared peripheral blood cytokine profiles in patients with CPA versus healthy controls and explored the relationship with disease severity. Methods: Interferon-gamma (IFNγ), interleukin (IL)-17, tumor necrosis factor-α, IL-6, IL-12, and IL-10 were measured after in vitro stimulation of whole blood with lipopolysaccharide (LPS), phytohemagglutinin, β-glucan, zymosan (ZYM), IL-12 or IL-18, and combinations. Clinical parameters and mortality were correlated with cytokine production. Results: Cytokine profiles were evaluated in 133 patients (57.1% male, mean age 61 years). In comparison to controls, patients with CPA had significantly reduced production of IFNγin response to stimulation with β-glucan+IL-12 (312 vs 988 pg/mL), LPS+IL-12 (252 vs 1033 pg/mL), ZYM+IL-12 (996 vs 2347 pg/mL), and IL-18+IL-12 (7193 vs 12 330 pg/mL). Age>60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.00-2.91; P=.05) and chronic obstructive pulmonary disease (HR, 1.69; 95% CI, 1.03-2.78; P=.039) were associated with worse survival, whereas high IFNγproduction in response to beta-glucan+IL-12 stimulation (HR, 0.48; 95% CI,. 25-0.92; P=.026) was associated with reduced mortality. Conclusions: Patients with CPA show impaired IFNγproduction in peripheral blood in response to stimuli. Defective IFNγproduction ability correlates with worse outcomes. Immunotherapy with IFNγcould be beneficial for patients showing impaired IFNγproduction in CPA.
