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. 2000 Jan;55(1):46–52. doi: 10.1136/thorax.55.1.46

Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls

T Bauer 1, C Monton 1, A Torres 1, H Cabello 1, X Fillela 1, A Maldonado 1, J Nicolas 1, E Zavala 1
PMCID: PMC1745592  PMID: 10607801

Abstract

BACKGROUND—The inflammatory response has been widely investigated in patients with acute respiratory distress syndrome (ARDS) and pneumonia. Studies investigating the diagnostic values of serum cytokine levels have yielded conflicting results and only little information is available for the differential diagnosis between ARDS and pneumonia.
METHODS—Clinical and physiological data, serum concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and quantitative cultures of lower respiratory tract specimens were obtained from 46 patients with ARDS and 20 with severe pneumonia within 24 hours of the onset of the disease and from 10 control subjects with no inflammatory lung disease. Cytokine concentrations were compared between groups and determinants in addition to the diagnosis were tested.
RESULTS—Serum TNF-α levels were significantly higher in ARDS patients (67 (57) pg/ml) than in patients with severe pneumonia (35 (20) pg/ml; p = 0.031) or controls (17 (8) pg/ml; p = 0.007). For IL-1β and IL-6 the observed differences were not statistically significant between patients with ARDS (IL-1β: 34 (65) pg/ml; IL-6: 712 (1058) pg/ml), those with severe pneumonia (IL-1β: 3 (4) pg/ml, p = 0.071; IL-6: 834 (1165) pg/ml, p = 1.0), and controls (IL-1β: 6 (11) pg/ml, p = 0.359; IL-6: 94 (110) pg/ml, p = 0.262). TNF-α (standardised coefficient β = 0.410, p<0.001) and IL-1β (standardised coefficient β = 0.311, p = 0.006) were most strongly associated with the degree of lung injury, even when the diagnostic group was included in the statistical model.
CONCLUSIONS—Serum TNF-α levels were higher in patients with ARDS than in those with severe pneumonia or in control subjects. Multivariate results suggest that the levels of systemic TNF-α and IL-1β reflect the severity of the lung injury rather than the diagnosis.



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Selected References

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  1. Armstrong L., Millar A. B. Relative production of tumour necrosis factor alpha and interleukin 10 in adult respiratory distress syndrome. Thorax. 1997 May;52(5):442–446. doi: 10.1136/thx.52.5.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernard G. R., Artigas A., Brigham K. L., Carlet J., Falke K., Hudson L., Lamy M., Legall J. R., Morris A., Spragg R. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818–824. doi: 10.1164/ajrccm.149.3.7509706. [DOI] [PubMed] [Google Scholar]
  3. Calandra T., Baumgartner J. D., Grau G. E., Wu M. M., Lambert P. H., Schellekens J., Verhoef J., Glauser M. P. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis. 1990 May;161(5):982–987. doi: 10.1093/infdis/161.5.982. [DOI] [PubMed] [Google Scholar]
  4. Chastre J., Fagon J. Y., Bornet-Lecso M., Calvat S., Dombret M. C., al Khani R., Basset F., Gibert C. Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med. 1995 Jul;152(1):231–240. doi: 10.1164/ajrccm.152.1.7599829. [DOI] [PubMed] [Google Scholar]
  5. Dehoux M. S., Boutten A., Ostinelli J., Seta N., Dombret M. C., Crestani B., Deschenes M., Trouillet J. L., Aubier M. Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med. 1994 Sep;150(3):710–716. doi: 10.1164/ajrccm.150.3.8087341. [DOI] [PubMed] [Google Scholar]
  6. Donnelly S. C., Haslett C., Dransfield I., Robertson C. E., Carter D. C., Ross J. A., Grant I. S., Tedder T. F. Role of selectins in development of adult respiratory distress syndrome. Lancet. 1994 Jul 23;344(8917):215–219. doi: 10.1016/s0140-6736(94)92995-5. [DOI] [PubMed] [Google Scholar]
  7. Ewig S., Ruiz M., Mensa J., Marcos M. A., Martinez J. A., Arancibia F., Niederman M. S., Torres A. Severe community-acquired pneumonia. Assessment of severity criteria. Am J Respir Crit Care Med. 1998 Oct;158(4):1102–1108. doi: 10.1164/ajrccm.158.4.9803114. [DOI] [PubMed] [Google Scholar]
  8. Fox-Dewhurst R., Alberts M. K., Kajikawa O., Caldwell E., Johnson M. C., 2nd, Skerrett S. J., Goodman R. B., Ruzinski J. T., Wong V. A., Chi E. Y. Pulmonary and systemic inflammatory responses in rabbits with gram-negative pneumonia. Am J Respir Crit Care Med. 1997 Jun;155(6):2030–2040. doi: 10.1164/ajrccm.155.6.9196112. [DOI] [PubMed] [Google Scholar]
  9. Gattinoni L., Pelosi P., Suter P. M., Pedoto A., Vercesi P., Lissoni A. Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease. Different syndromes? Am J Respir Crit Care Med. 1998 Jul;158(1):3–11. doi: 10.1164/ajrccm.158.1.9708031. [DOI] [PubMed] [Google Scholar]
  10. Goodman R. B., Strieter R. M., Martin D. P., Steinberg K. P., Milberg J. A., Maunder R. J., Kunkel S. L., Walz A., Hudson L. D., Martin T. R. Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):602–611. doi: 10.1164/ajrccm.154.3.8810593. [DOI] [PubMed] [Google Scholar]
  11. Headley A. S., Tolley E., Meduri G. U. Infections and the inflammatory response in acute respiratory distress syndrome. Chest. 1997 May;111(5):1306–1321. doi: 10.1378/chest.111.5.1306. [DOI] [PubMed] [Google Scholar]
  12. Hyers T. M., Tricomi S. M., Dettenmeier P. A., Fowler A. A. Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1991 Aug;144(2):268–271. doi: 10.1164/ajrccm/144.2.268. [DOI] [PubMed] [Google Scholar]
  13. Kelley J. Cytokines of the lung. Am Rev Respir Dis. 1990 Mar;141(3):765–788. doi: 10.1164/ajrccm/141.3.765. [DOI] [PubMed] [Google Scholar]
  14. Kiehl M. G., Ostermann H., Thomas M., Müller C., Cassens U., Kienast J. Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome. Crit Care Med. 1998 Jul;26(7):1194–1199. doi: 10.1097/00003246-199807000-00019. [DOI] [PubMed] [Google Scholar]
  15. Le Gall J. R., Lemeshow S., Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993 Dec 22;270(24):2957–2963. doi: 10.1001/jama.270.24.2957. [DOI] [PubMed] [Google Scholar]
  16. Marks J. D., Marks C. B., Luce J. M., Montgomery A. B., Turner J., Metz C. A., Murray J. F. Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration. Am Rev Respir Dis. 1990 Jan;141(1):94–97. doi: 10.1164/ajrccm/141.1.94. [DOI] [PubMed] [Google Scholar]
  17. Maus U., Rosseau S., Knies U., Seeger W., Lohmeyer J. Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. Eur Respir J. 1998 Mar;11(3):534–541. [PubMed] [Google Scholar]
  18. Meduri G. U., Headley S., Kohler G., Stentz F., Tolley E., Umberger R., Leeper K. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest. 1995 Apr;107(4):1062–1073. doi: 10.1378/chest.107.4.1062. [DOI] [PubMed] [Google Scholar]
  19. Meduri G. U., Headley S., Tolley E., Shelby M., Stentz F., Postlethwaite A. Plasma and BAL cytokine response to corticosteroid rescue treatment in late ARDS. Chest. 1995 Nov;108(5):1315–1325. doi: 10.1378/chest.108.5.1315. [DOI] [PubMed] [Google Scholar]
  20. Meduri G. U., Kohler G., Headley S., Tolley E., Stentz F., Postlethwaite A. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest. 1995 Nov;108(5):1303–1314. doi: 10.1378/chest.108.5.1303. [DOI] [PubMed] [Google Scholar]
  21. Millar A. B., Foley N. M., Singer M., Johnson N. M., Meager A., Rook G. A. Tumour necrosis factor in bronchopulmonary secretions of patients with adult respiratory distress syndrome. Lancet. 1989 Sep 23;2(8665):712–714. doi: 10.1016/s0140-6736(89)90772-1. [DOI] [PubMed] [Google Scholar]
  22. Moussa K., Michie H. J., Cree I. A., McCafferty A. C., Winter J. H., Dhillon D. P., Stephens S., Brown R. A. Phagocyte function and cytokine production in community acquired pneumonia. Thorax. 1994 Feb;49(2):107–111. doi: 10.1136/thx.49.2.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Murray J. F., Matthay M. A., Luce J. M., Flick M. R. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Sep;138(3):720–723. doi: 10.1164/ajrccm/138.3.720. [DOI] [PubMed] [Google Scholar]
  24. Nelson S., Mason C. M., Kolls J., Summer W. R. Pathophysiology of pneumonia. Clin Chest Med. 1995 Mar;16(1):1–12. [PubMed] [Google Scholar]
  25. Parsons P. E., Moore F. A., Moore E. E., Iklé D. N., Henson P. M., Worthen G. S. Studies on the role of tumor necrosis factor in adult respiratory distress syndrome. Am Rev Respir Dis. 1992 Sep;146(3):694–700. doi: 10.1164/ajrccm/146.3.694. [DOI] [PubMed] [Google Scholar]
  26. Pugin J., Verghese G., Widmer M. C., Matthay M. A. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med. 1999 Feb;27(2):304–312. doi: 10.1097/00003246-199902000-00036. [DOI] [PubMed] [Google Scholar]
  27. Roten R., Markert M., Feihl F., Schaller M. D., Tagan M. C., Perret C. Plasma levels of tumor necrosis factor in the adult respiratory distress syndrome. Am Rev Respir Dis. 1991 Mar;143(3):590–592. doi: 10.1164/ajrccm/143.3.590. [DOI] [PubMed] [Google Scholar]
  28. Schütte H., Lohmeyer J., Rosseau S., Ziegler S., Siebert C., Kielisch H., Pralle H., Grimminger F., Morr H., Seeger W. Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe pneumonia and cardiogenic pulmonary oedema. Eur Respir J. 1996 Sep;9(9):1858–1867. doi: 10.1183/09031936.96.09091858. [DOI] [PubMed] [Google Scholar]
  29. Seidenfeld J. J., Pohl D. F., Bell R. C., Harris G. D., Johanson W. G., Jr Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1986 Jul;134(1):12–16. doi: 10.1164/arrd.1986.134.1.12. [DOI] [PubMed] [Google Scholar]
  30. Sloane P. J., Gee M. H., Gottlieb J. E., Albertine K. H., Peters S. P., Burns J. R., Machiedo G., Fish J. E. A multicenter registry of patients with acute respiratory distress syndrome. Physiology and outcome. Am Rev Respir Dis. 1992 Aug;146(2):419–426. doi: 10.1164/ajrccm/146.2.419. [DOI] [PubMed] [Google Scholar]
  31. Suter P. M., Suter S., Girardin E., Roux-Lombard P., Grau G. E., Dayer J. M. High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis. 1992 May;145(5):1016–1022. doi: 10.1164/ajrccm/145.5.1016. [DOI] [PubMed] [Google Scholar]
  32. Torres A., el-Ebiary M., Padró L., Gonzalez J., de la Bellacasa J. P., Ramirez J., Xaubet A., Ferrer M., Rodriguez-Roisin R. Validation of different techniques for the diagnosis of ventilator-associated pneumonia. Comparison with immediate postmortem pulmonary biopsy. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):324–331. doi: 10.1164/ajrccm.149.2.8306025. [DOI] [PubMed] [Google Scholar]
  33. Wimberley N., Faling L. J., Bartlett J. G. A fiberoptic bronchoscopy technique to obtain uncontaminated lower airway secretions for bacterial culture. Am Rev Respir Dis. 1979 Mar;119(3):337–343. doi: 10.1164/arrd.1979.119.3.337. [DOI] [PubMed] [Google Scholar]
  34. el-Ebiary M., Torres A., González J., de la Bellacasa J. P., García C., Jiménez de Anta M. T., Ferrer M., Rodriguez-Roisin R. Quantitative cultures of endotracheal aspirates for the diagnosis of ventilator-associated pneumonia. Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1552–1557. doi: 10.1164/ajrccm/148.6_Pt_1.1552. [DOI] [PubMed] [Google Scholar]

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