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

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.

Figure 1

A, Multidimensional scaling in two dimensions that provides a visualization of similarities or dissimilarities among cytokine and markers and cause. B, Hierarchic cluster analysis for assigning microorganisms into cluster groups that are more similar to one or another in other clusters. CHLAM = chlamydophila; COXBU = Coxiella burnetii; ENTER = Enterobacteriaceae; HAEIN = Haemophilus influenzae; INFLU = influenza virus; LEGPN = Legionella pneumophila; MYCOP = Mycoplasma pneumoniae; PSAER = Pseudomonas aeruginosa; STAAU = Staphylococcus aureus; STPNE = Streptococcus pneumoniae; UNKNO = unknown cause.