Concurrent Immune Suppression and Hyperinflammation in Patients With Community-Acquired Pneumonia

Abstract

Background: The nature and timing of the host immune response during infections remain uncertain and most knowledge is derived from critically ill sepsis patients. We aimed to test the hypothesis that community-acquired pneumonia (CAP) is associated with concurrent immune suppression and systemic inflammation. Methods: Blood was collected from 79 CAP patients within 24 h after hospitalization and 1 month after discharge; 42 age-and sex-matched subjects without acute infection served as controls. Blood leukocytes were stimulated with lipopolysaccharide (LPS) or Klebsiella pneumoniae, and cytokines were measured in supernatants. Fifteen plasma biomarkers reflective of key host response pathways were compared between CAP patients with the strongest immune suppression (lowest 25% blood leukocyte tumor necrosis factor (TNF)-α production in response to LPS) and those with the least immune suppression (highest 25% of LPS-induced TNF-α production). Results: Blood leukocytes of CAP patients (relative to control subjects) showed a reduced capacity to release TNF-α, interleukin (IL)-1β, IL-6 and IL-10 upon stimulation with LPS or K. pneumoniae, with a concurrently enhanced ability to release the antiinflammatory mediator IL-1 receptor antagonist, irrespective of the presence of sepsis (18.9% of cases). Low (relative to high) TNF-α producers displayed higher plasma levels of biomarkers reflecting systemic inflammation, neutrophil degranulation, endothelial cell activation, a disturbed vascular barrier function and coagulation activation. Conclusion: CAP replicates a common feature of immune suppression in sepsis. The coexistence of immune suppression and hyperinflammation in CAP argues against the theory of two distinct phases during the host response to sepsis.

The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

“…However, no statistically significant association between the COVID-19 status and IL-10 was observed, which may be explained either by the fact that IL-10 is not the only or main driver of the length of MV in COVID-19 patients, either by a lack of statistical power, or both. As recently described, concurrent immune suppression and hyperinflammation are a hallmark of the pathogenesis in non-COVID-19 CAP, and argue against two distinct phases of host response [42]. Nevertheless, in COVID-19 patients, we observed higher IL-6:IL-10 and TNF-α:IL-10 ratios that could reflect an unbalanced overproduction of IL-10.…”

Rectal bacteriome and virome signatures and clinical outcomes in community-acquired pneumonia: An exploratory study

“…Participants were recruited as part of the ELDER-BIOME study. Details of recruitment and data collection have been previously published [21] . In short, consecutive patients older than 18 years admitted to a university (Amsterdam UMC, location Academic Medical Centre) or community hospital (BovenIJ hospital) in the Netherlands between October 2016 and July 2018, with the clinical suspicion of a community-acquired pneumonia were included, defined as at least one respiratory symptom (new cough or sputum production, chest pain, dyspnea, tachypnea, abnormal lung examination, or respiratory failure) and one systemic symptom (documented fever or hypothermia, leukocytosis or leukopenia) and had an evident new or progressive infiltrate, consolidation, cavitation, or pleural effusion on chest X-ray or computed tomography scan.…”

Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study

“…Details of recruitment have been published previously [ 17 ]. In brief, consecutive patients older than 18 years admitted to the Amsterdam UMC, location Academic Medical Center (AMC) or BovenIJ hospital in the Netherlands during the influenza seasons (October 2016 to June 2017 and October 2017 to June 2018) were screened by trained research physicians.…”