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Original Research: CHEST INFECTIONS |

Cytokine Activation Patterns and Biomarkers Are Influenced by Microorganisms in Community-Acquired PneumoniaMicroorganisms, Cytokine Patterns, and Pneumonia

Rosario Menéndez, PhD; José Miguel Sahuquillo-Arce, MD; Soledad Reyes, MD; Raquel Martínez, MD; Eva Polverino, PhD; Catia Cillóniz, MD; Juan Ginés Córdoba, PhD; Beatriz Montull, MD; Antoni Torres, MD, PhD, FCCP
Author and Funding Information

From Servicio de Neumología (Drs Menéndez, Reyes, Martínez, and Montull) and Servicio de Microbiología (Drs Sahuquillo-Arce and Córdoba), Hospital Universitari i Politècnic La Fe, Valencia; and Servei de Pneumologia (Drs Polverino, Cillóniz, and Torres), Institut del Tòrax, Hospital Clinic, IDIBAPS, CIBERES, Universitat de Barcelona, Barcelona, Spain.

Correspondence to: Rosario Menéndez, PhD, Department of Pneumology, Hospital Universitari i Politècnic La Fe, Bulevar Sur s/n, 46026 Valencia, Spain; e-mail: rosmenend@gmail.com


Funding/Support: The study was funded by Centro Investigación Biomedica en Red de Enfermedades Respiratorias, an initiative of Instituto de Salud Carlos III; Sociedad Española de Neumología y Cirugía Torácica [Grant 2003]; Fondo de Investigación Sanitario [Grant PI041136]; Fondo de Investigación Sanitario [Grant PI080727]; and an IMPULSA grant.

Drs Menéndez and Sahuquillo-Arce are considered as first authors.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


© 2012 American College of Chest Physicians


Chest. 2012;141(6):1537-1545. doi:10.1378/chest.11-1446
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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.

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