title: 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.
authors.affiliation: Servicio de Neumología, Hospital Universitari i Politècnic La Fe, Valencia, Spain. Electronic address: rosmenend@gmail.com.
authors.forename: Rosario
authors.initials: R
authors.lastname: Menéndez
authors.affiliation: Servicio de Microbiología, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sahuquillo-Arce
authors.affiliation: Servicio de Neumología, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Reyes
authors.affiliation: Servicio de Neumología, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Martínez
authors.affiliation: Servei de Pneumologia, Institut del Tòrax, Hospital Clinic, IDIBAPS, CIBERES, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Polverino
authors.affiliation: Servei de Pneumologia, Institut del Tòrax, Hospital Clinic, IDIBAPS, CIBERES, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Catia
authors.initials: C
authors.lastname: Cillóniz
authors.affiliation: Servicio de Microbiología, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: Juan Ginés
authors.initials: JG
authors.lastname: Córdoba
authors.affiliation: Servicio de Neumología, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Montull
authors.affiliation: Servei de Pneumologia, Institut del Tòrax, Hospital Clinic, IDIBAPS, CIBERES, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D017714:Community-Acquired Infections / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D016207:Cytokines; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide