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Published in: Intensive Care Medicine 1/2004

01-01-2004 | Original

Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia

Authors: Julian L. Millo, Marcus J. Schultz, Conrad Williams, Gerrit J. Weverling, Timothy Ringrose, Carolyn I. Mackinlay, Tom van der Poll, Christopher S. Garrard

Published in: Intensive Care Medicine | Issue 1/2004

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Abstract

Objective

To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP).

Design

Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) α, interleukin (IL)-1α, IL-1β, IL-6, and IL-10 and the cytokine inhibitors soluble TNFα receptor type I (sTNFαRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA.

Setting

An adult medical and surgical university hospital intensive care unit.

Patients

Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls.

Interventions

None.

Results

Plasma concentrations of the measured cytokines and cytokine inhibitors did not change significantly in any patients. In control patients, NBL fluid concentrations of sIL-1RII decreased significantly over time (P=0.01). In patients who developed VAP, NBL fluid concentrations of TNFα, sTNFαRI, IL-1α, and IL-1β increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/plasma concentration ratios for TNFα, sTNFαRI, IL-1α, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001, P=0.001, P=0.04, P=0.03, and P=0.04, respectively).

Conclusion

Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.
Literature
1.
go back to reference Strausbaugh L (2000) Nosocomial respiratory infections. In: Mandell G, Bennet J, Dolin R (eds) Principles and practice of infectious disease. Churchill Livingstone, St Louis, USA, pp 3020–3028 Strausbaugh L (2000) Nosocomial respiratory infections. In: Mandell G, Bennet J, Dolin R (eds) Principles and practice of infectious disease. Churchill Livingstone, St Louis, USA, pp 3020–3028
2.
go back to reference Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903CrossRef Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903CrossRef
3.
go back to reference Mehrad B, Standiford TJ (1999) Role of cytokines in pulmonary antimicrobial host defense. Immunol Res 20:15–27CrossRef Mehrad B, Standiford TJ (1999) Role of cytokines in pulmonary antimicrobial host defense. Immunol Res 20:15–27CrossRef
4.
go back to reference Schultz M, Knapp S, van der Poll T (2002) Regulatory role of alveolar macrophages in pulmonary host defense. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine. Springer, Berlin Heidelberg New York, pp 65–76 Schultz M, Knapp S, van der Poll T (2002) Regulatory role of alveolar macrophages in pulmonary host defense. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine. Springer, Berlin Heidelberg New York, pp 65–76
5.
go back to reference Nelson S, Bagby GJ, Bainton BG, Wilson LA, Thompson JJ, Summer WR (1989) Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis 159:189–194CrossRef Nelson S, Bagby GJ, Bainton BG, Wilson LA, Thompson JJ, Summer WR (1989) Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis 159:189–194CrossRef
6.
go back to reference Tutor JD, Mason CM, Dobard E, Beckerman RC, Summer WR, Nelson S (1994) Loss of compartmentalization of alveolar tumor necrosis factor after lung injury. Am J Respir Crit Care Med 149:1107–1111CrossRef Tutor JD, Mason CM, Dobard E, Beckerman RC, Summer WR, Nelson S (1994) Loss of compartmentalization of alveolar tumor necrosis factor after lung injury. Am J Respir Crit Care Med 149:1107–1111CrossRef
7.
go back to reference Kurahashi K, Kajikawa O, Sawa T, Ohara M, Gropper MA, Frank DW, Martin TR, Wiener-Kronish JP (1999) Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 104:743–750CrossRef Kurahashi K, Kajikawa O, Sawa T, Ohara M, Gropper MA, Frank DW, Martin TR, Wiener-Kronish JP (1999) Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 104:743–750CrossRef
8.
go back to reference Dehoux MS, Boutten A, Ostinelli J, Seta N, Dombret MC, Crestani B, Deschenes M, Trouillet JL, Aubier M (1994) Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 150:710–716CrossRef Dehoux MS, Boutten A, Ostinelli J, Seta N, Dombret MC, Crestani B, Deschenes M, Trouillet JL, Aubier M (1994) Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 150:710–716CrossRef
9.
go back to reference Boutten A, Dehoux MS, Seta N, Ostinelli J, Venembre P, Crestani B, Dombret MC, Durand G, Aubier M (1996) Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 153:336–342CrossRef Boutten A, Dehoux MS, Seta N, Ostinelli J, Venembre P, Crestani B, Dombret MC, Durand G, Aubier M (1996) Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 153:336–342CrossRef
10.
go back to reference Glynn P, Coakley R, Kilgallen I, Murphy N, O’Neill S (1999) Circulating interleukin 6 and interleukin 10 in community acquired pneumonia. Thorax 54:51–55CrossRef Glynn P, Coakley R, Kilgallen I, Murphy N, O’Neill S (1999) Circulating interleukin 6 and interleukin 10 in community acquired pneumonia. Thorax 54:51–55CrossRef
11.
go back to reference Bauer TT, Monton C, Torres A, Cabello H, Fillela X, Maldonado A, Nicolas JM, Zavala E (2000) Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls. Thorax 55:46–52CrossRef Bauer TT, Monton C, Torres A, Cabello H, Fillela X, Maldonado A, Nicolas JM, Zavala E (2000) Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls. Thorax 55:46–52CrossRef
12.
go back to reference Friedland JS, Porter JC, Daryanani S, Bland JM, Screaton NJ, Vesely MJ, Griffin GE, Bennett ED, Remick DG (1996) Plasma proinflammatory cytokine concentrations, Acute Physiology and Chronic Health Evaluation (APACHE) III scores and survival in patients in an intensive care unit. Crit Care Med 24:1775–1781CrossRef Friedland JS, Porter JC, Daryanani S, Bland JM, Screaton NJ, Vesely MJ, Griffin GE, Bennett ED, Remick DG (1996) Plasma proinflammatory cytokine concentrations, Acute Physiology and Chronic Health Evaluation (APACHE) III scores and survival in patients in an intensive care unit. Crit Care Med 24:1775–1781CrossRef
13.
go back to reference Bonten MJ, Froon AH, Gaillard CA, Greve JW, de Leeuw PW, Drent M, Stobberingh, EE, Buurman WA (1997) The systemic inflammatory response in the development of ventilator-associated pneumonia. Am J Respir Crit Care Med 156:1105–1113CrossRef Bonten MJ, Froon AH, Gaillard CA, Greve JW, de Leeuw PW, Drent M, Stobberingh, EE, Buurman WA (1997) The systemic inflammatory response in the development of ventilator-associated pneumonia. Am J Respir Crit Care Med 156:1105–1113CrossRef
14.
go back to reference A’Court CH, Garrard CS, Crook D, Bowler I, Conlon C, Peto T, Anderson E (1993) Microbiological lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture. Q J Med 86:635–648CrossRef A’Court CH, Garrard CS, Crook D, Bowler I, Conlon C, Peto T, Anderson E (1993) Microbiological lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture. Q J Med 86:635–648CrossRef
15.
go back to reference Garrard CS, A’Court CD (1995) The diagnosis of pneumonia in the critically ill. Chest 108:17S-25SCrossRef Garrard CS, A’Court CD (1995) The diagnosis of pneumonia in the critically ill. Chest 108:17S-25SCrossRef
16.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829CrossRef Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829CrossRef
17.
go back to reference Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ (1995) Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med 23:1638–1652CrossRef Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ (1995) Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med 23:1638–1652CrossRef
18.
go back to reference Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall, JR, Morris A, Spragg R (1994) Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med 20:225–232CrossRef Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall, JR, Morris A, Spragg R (1994) Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med 20:225–232CrossRef
19.
go back to reference van Deuren M, van der Ven-Jongekrijg J, Vannier E, van Dalen R, Pesman G, Bartelink AK, Dinarello CA, van der Meer JW (1997) The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections. Blood 90:1101–1108CrossRef van Deuren M, van der Ven-Jongekrijg J, Vannier E, van Dalen R, Pesman G, Bartelink AK, Dinarello CA, van der Meer JW (1997) The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections. Blood 90:1101–1108CrossRef
Metadata
Title
Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia
Authors
Julian L. Millo
Marcus J. Schultz
Conrad Williams
Gerrit J. Weverling
Timothy Ringrose
Carolyn I. Mackinlay
Tom van der Poll
Christopher S. Garrard
Publication date
01-01-2004
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 1/2004
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-003-2060-0

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