期刊论文详细信息
BMC Pulmonary Medicine
Interleukin 6, lipopolysaccharide-binding protein and interleukin 10 in the prediction of risk and etiologic patterns in patients with community-acquired pneumonia: results from the German competence network CAPNETZ
Frank Bühling6  Tobias Welte2  Michael Prediger5  Santiago Ewig3  Mathias W Pletz4  Peter Martus1  Katrin Zobel5 
[1] Department of Biometry and Clinical Epidemiologie, Charité, Chariteplatz 1, 10098 Berlin, Germany;Department of Pneumology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany;Thoraxzentrum Ruhrgebiet, Respiratory and Infectious Diseases, Ev. Krankenhaus Herne und Augusta-Kranken-Anstalt, Bochum, Thoraxzentrum Ruhrgebiet, Hordeler Strasse 7-9, 44651 Herne, Germany;Division of Gastroenterology, Hepatology and Infectious Diseases, Jena University Hospital, Hospital Erlanger Allee 101, 07740 Jena, Germany;Department of Pneumology, Carl-Thiem-Klinikum Cottbus, Thiemstrasse 111, 03048 Cottbus, Germany;Department of Laboratory Medicine, Carl-Thiem-Klinikum Cottbus, Thiemstrasse 111, 03048 Cottbus, Germany
关键词: Cytokine;    Biomarker;    Pneumonia;    CAP;    LBP;    Interleukin-10;    Interleukin-6;   
Others  :  1172492
DOI  :  10.1186/1471-2466-12-6
 received in 2011-07-12, accepted in 2012-02-20,  发布年份 2012
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【 摘 要 】

Background

The aim of our study was to investigate the predictive value of the biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10) and lipopolysaccharide-binding protein (LBP) compared with clinical CRB and CRB-65 severity scores in patients with community-acquired pneumonia (CAP).

Methods

Samples and data were obtained from patients enrolled into the German CAPNETZ study group. Samples (blood, sputum and urine) were collected within 24 h of first presentation and inclusion in the CAPNETZ study, and CRB and CRB-65 scores were determined for all patients at the time of enrollment. The combined end point representative of a severe course of CAP was defined as mechanical ventilation, intensive care unit treatment and/or death within 30 days. Overall, a total of 1,000 patients were enrolled in the study. A severe course of CAP was observed in 105 (10.5%) patients.

Results

The highest IL-6, IL-10 and LBP concentrations were found in patients with CRB-65 scores of 3-4 or CRB scores of 2-3. IL-6 and LBP levels on enrollment in the study were significantly higher for patients with a severe course of CAP than for those who did not have severe CAP. In receiver operating characteristic analyses, the area under the curve values for of IL-6 (0.689), IL-10 (0.665) and LPB (0.624) in a severe course of CAP were lower than that of CRB-65 (0.764) and similar to that of CRB (0.69). The accuracy of both CRB and CRB-65 was increased significantly by including IL-6 measurements. In addition, higher cytokine concentrations were found in patients with typical bacterial infections compared with patients with atypical or viral infections and those with infection of unknown etiology. LBP showed the highest discriminatory power with respect to the etiology of infection.

Conclusions

IL-6, IL-10 and LBP concentrations were increased in patients with a CRB-65 score of 3-4 and a severe course of CAP. The concentrations of IL-6 and IL-10 reflected the severity of disease in patients with CAP. The predictive power of IL-6, IL-10 and LBP for a severe course of pneumonia was lower than that of CRB-65. Typical bacterial pathogens induced the highest LBP, IL-6 and IL-10 concentrations.

【 授权许可】

   
2012 Zobel et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Welte T, Suttorp N, Marre R: CAPNETZ-community-acquired pneumonia competence network. Infection 2004, 32:234-238.
  • [2]Almirall J, Bolibar I, Vidal J, Sauca G, Coll P, Niklasson B, Bartolome M, Balanzo X: Epidemiology of community-acquired pneumonia in adults: a population-based study. Eur Respir J 2000, 15:757-763.
  • [3]Ewig S, Torres A, Woodhead M: Assessment of pneumonia severity: a European perspective. Eur Respir J 2006, 27:6-8.
  • [4]Bauer TT, Ewig S, Marre R, Suttorp N, Welte T: CRB-65 predicts death from community-acquired pneumonia. J Intern Med 2006, 260:93-101.
  • [5]Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F: Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003, 374:1-20.
  • [6]Grutz G: New insights into the molecular mechanism of interleukin-10-mediated immunosuppression. J Leukoc Biol 2005, 77:3-15.
  • [7]Schumann RR, Zweigner J: A novel acute-phase marker: lipopolysaccharide binding protein (LBP). Clin Chem Lab Med 1999, 37:271-274.
  • [8]Jones SA: Directing transition from innate to acquired immunity: defining a role for IL-6. J Immunol 2005, 175:3463-3468.
  • [9]Fischer CP: Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 2006, 12:6-33.
  • [10]Kruger S, Ewig S, Marre R, Papassotiriou J, Richter K, von Baum H, Suttorp N, Welte T: Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes. Eur Respir J 2008, 31:349-355.
  • [11]Kruger S, Ewig S, Papassotiriou J, Kunde J, Marre R, von Baum H, Suttor N, Welte T: Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP: results from the German competence network CAPNETZ. Respir Res 2009, 10:65. BioMed Central Full Text
  • [12]Infektionen der tiefen Atemwege: Quality standards for microbiological diagnostic techniques for infectious diseases. Edited by Mauch H, Lütticken R, Gatermann S. Munich: Urban & Fischer Verlag; 2000:2011.
  • [13]Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS: Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008, 27:157-172.
  • [14]Pencina MJ, D'Agostino RB Sr, Steyerberg EW: Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 2011, 30:11-21.
  • [15]DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988, 44:837-845.
  • [16]Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN: A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997, 336:243-250.
  • [17]Capelastegui A, Espana PP, Quintana JM, Areitio I, Gorordo I, Egurrola M, Bilbao A: Validation of a predictive rule for the management of community-acquired pneumonia. Eur Respir J 2006, 27:151-157.
  • [18]Buising KL, Thursky KA, Black JF, MacGregor L, Street AC, Kennedy MP, Brown GV: A prospective comparison of severity scores for identifying patients with severe community acquired pneumonia: reconsidering what is meant by severe pneumonia. Thorax 2006, 61:419-424.
  • [19]Kruger S, Ewig S, Kunde J, Hartmann O, Suttorp N, Welte T: Pro-atrial natriuretic peptide and pro-vasopressin for predicting short-term and long-term survival in community-acquired pneumonia: results from the German Competence Network CAPNETZ. Thorax 2010, 65:208-214.
  • [20]Kruger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T: Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med 2010, 182:1426-1434.
  • [21]Dehoux MS, Boutten A, Ostinelli J, Seta N, Dombret MC, Crestani B, Deschenes M, Trouillet JL, Aubier M: Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 1994, 150:710-716.
  • [22]Kolsuz M, Erginel S, Alatas O, Alatas F, Metintas M, Ucgun I, Harmanci E, Colak O: Acute phase reactants and cytokine levels in unilateral community-acquired pneumonia. Respiration 2003, 70:615-622.
  • [23]Wu CL, Chan MC, Chang GC, Lee YL, Chin CS, Chang KM, Hsu JY: Etiology and cytokine expression in patients requiring mechanical ventilation due to severe community-acquired pneumonia. J Formos Med Assoc 2006, 105:49-55.
  • [24]Fernandez-Serrano S, Dorca J, Coromines M, Carratala J, Gudiol F, Manresa F: Molecular inflammatory responses measured in blood of patients with severe community-acquired pneumonia. Clin Diagn Lab Immunol 2003, 10:813-820.
  • [25]Opal SM, Scannon PJ, Vincent JL, White M, Carroll SF, Palardy JE, Parejo NA, Pribble JP, Lemke JH: Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis 1999, 180:1584-1589.
  • [26]Blairon L, Wittebole X, Laterre PF: Lipopolysaccharide-binding protein serum levels in patients with severe sepsis due to gram-positive and fungal infections. J Infect Dis 2003, 187:287-291.
  • [27]Masia M, Gutierrez F, Padilla S, Soldan B, Mirete C, Shum C, Hernandez I, Royo G, Martin-Hidalgo A: Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors. Clin Microbiol Infect 2007, 13:153-161.
  • [28]Tejera A, Santolaria F, Diez ML, Aleman-Valls MR, Gonzalez-Reimers E, Martinez-Riera A, Milena-Abril A: Prognosis of community acquired pneumonia (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other mediators of the inflammatory response. Cytokine 2007, 38:117-123.
  • [29]Ware JH: The limitations of risk factors as prognostic tools. N Engl J Med 2006, 355:2615-2617.
  • [30]Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, Fine J, Krichevsky A, Delude RL, Angus DC: Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med 2007, 167:1655-1663.
  • [31]Taniguchi T, Koido Y, Aiboshi J, Yamashita T, Suzaki S, Kurokawa A: Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. Crit Care Med 1999, 27:1262-1264.
  • [32]Lekkou A, Karakantza M, Mouzaki A, Kalfarentzos F, Gogos CA: Cytokine production and monocyte HLA-DR expression as predictors of outcome for patients with community-acquired severe infections. Clin Diagn Lab Immunol 2004, 11:161-167.
  • [33]Ewig S, Torres A, Angeles MM, Angrill J, Rano A, de Roux A, Mensa J, Martinez JA, de la Bellacasa JP, Bauer T: Factors associated with unknown aetiology in patients with community-acquired pneumonia. Eur Respir J 2002, 20:1254-1262.
  • [34]Schultz MJ: Cytokines and host defense in pneumonia. In Intensivmedizin und Notfallmedizin, Band 36, Heft 3. Darmstadt: Steinkopff-Verlag; 1999.
  • [35]Menendez R, Cavalcanti M, Reyes S, Mensa J, Martinez R, Marcos MA, Filella X, Niederman M, Torres A: Markers of treatment failure in hospitalised community acquired pneumonia. Thorax 2008, 63:447-452.
  • [36]Menendez R, Torres A: Treatment failure in community-acquired pneumonia. Chest 2007, 132:1348-1355.
  • [37]Masia M, Gutierrez F, Llorca B, Navarro JC, Mirete C, Padilla S, Hernandez I, Flores E: Serum concentrations of lipopolysaccharide-binding protein as a biochemical marker to differentiate microbial etiology in patients with community-acquired pneumonia. Clin Chem 2004, 50:1661-1664.
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