Cytokine activation patterns and biomarkers are influenced by microorganisms in community-acquired pneumonia

Chest. 2012 Jun;141(6):1537-1545. doi: 10.1378/chest.11-1446. Epub 2011 Dec 22.

Abstract

Background: The inflammatory response in community-acquired pneumonia (CAP) depends on the host and on the challenge of the causal microorganism. Here, we analyze the patterns of inflammatory cytokines, procalcitonin (PCT), and C-reactive protein (CRP) in order to determine their diagnostic value.

Methods: This was a prospective study of 658 patients admitted with CAP. PCT and CRP were analyzed by immunoluminometric and immunoturbidimetric assays. Cytokines (tumor necrosis factor-α [TNF-α], IL-1β, IL-6, IL-8, and IL-10) were measured using enzyme immunoassay.

Results: The lowest medians of CRP, PCT, TNF-α, and IL-6 were found in CAP of unknown cause, and the highest were found in patients with positive blood cultures. Different cytokine profiles and biomarkers were found depending on cause: atypical bacteria (lower PCT and IL-6), viruses (lower PCT and higher IL-10), Enterobacteriaceae (higher IL-8), Streptococcus pneumoniae (high PCT), and Legionella pneumophila (higher CRP and TNF-α). PCT ≥ 0.36 mg/dL to predict positive blood cultures showed sensitivity of 85%, specificity of 42%, and negative predictive value (NPV) of 98%, whereas a cutoff of ≤ 0.5 mg/dL to predict viruses or atypicals vs bacteria showed sensitivity of 89%/81%, specificity of 68%/68%, positive predictive value of 12%/22%, and NPV of 99%/97%. In a multivariate Euclidean distance model, the lowest inflammatory expression was found in unknown cause and the highest was found in L pneumophila, S pneumoniae, and Enterobacteriaceae. Atypical bacteria exhibit an inflammatory pattern closer to that of viruses.

Conclusions: Different inflammatory patterns elicited by different microorganisms may provide a useful tool for diagnosis. Recognizing these patterns provides additional information that may facilitate a broader understanding of host inflammatory response to microorganisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism*
  • Calcitonin / blood*
  • Calcitonin Gene-Related Peptide
  • Community-Acquired Infections / blood*
  • Community-Acquired Infections / diagnosis
  • Community-Acquired Infections / microbiology
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pneumonia / blood*
  • Pneumonia / diagnosis
  • Pneumonia / microbiology
  • Predictive Value of Tests
  • Prospective Studies
  • Protein Precursors / blood*
  • Sensitivity and Specificity
  • Statistics, Nonparametric

Substances

  • Biomarkers
  • CALCA protein, human
  • Cytokines
  • Protein Precursors
  • Calcitonin
  • C-Reactive Protein
  • Calcitonin Gene-Related Peptide