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Methods: Interferon-gamma (IFNγ), IL-17, TNFα, IL-6, IL-12 and IL-10 were measured after in vitro stimulation of whole blood with lipopolysaccharide (LPS), phytohaemagglutinin (PHA), 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 IFNγ in 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 12330 pg/ml). Age >60 (p=0.05, HR 1.71, 95%CI 1.00-2.91) and COPD (p=0.039, HR 1.69, 95%CI 1.03-2.78) were associated with worse survival, whereas high IFNγ production in response to beta-glucan+IL-12 stimulation (p=0.026, HR 0.48, 95%CI 0.25-0.92) was associated with reduced mortality.
Conclusion: Patients with CPA show impaired IFNγ production in peripheral blood in response to stimuli. Defective IFNγ production ability correlates with worse outcomes. Immunotherapy with IFNγ could be beneficial for patients showing impaired IFNγ production in CPA.
Keywords: Chronic pulmonary aspergillosis, pathogenesis, cytokines, interferon-gamma, IL-17A, immunotherapy
|Journal||The Journal of Infectious Diseases|
|Publication status||Accepted/In press - 25 Nov 2021|
Research Beacons, Institutes and Platforms
- Lydia Becker Institute