Skip to main content
Top
Published in: Critical Care 6/2009

01-12-2009 | Commentary

Matrix metalloproteinases and their inhibitors: promising novel biomarkers in severe sepsis?

Authors: Ursula Hoffmann, Martina Brueckmann, Martin Borggrefe

Published in: Critical Care | Issue 6/2009

Login to get access

Abstract

The multicenter study conducted by Lorente and coworkers published in the previous issue of Critical Care demonstrates that matrix metalloproteinase (MMP)-9 and MMP-10 and their inhibitor tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are promising novel biomarkers to predict severity and outcome of sepsis. In recent years MMPs have emerged as biomarkers in a variety of diseases, such as sepsis, coronary artery disease, cancer, heart failure, chronic lung disease and rheumatoid arthritis. MMPs constitute a family of proteinases that are expressed during developmental, physiological, and pathophysiological processes, for example as a response to infection. Excessive inflammation following infection may cause tissue damage, and MMPs are implicated in causing this immunopathology. The activity of MMPs is regulated by secretion of specific inhibitors (TIMPs). Studies using MMP inhibitors and MMP knockout mice indicate that MMPs play an essential role in infection and in the host response to infection. The measurement of MMP-9 and MMP-10 and their inhibitor TIMP-1 in the intensive care setting could be an attractive noninvasive tool for determination of outcome of septic patients.
Literature
1.
go back to reference Lorente L, Martin MM, Labarta L, Diaz C, Solé-Violán J, Blanquer J, Orbe J, Rodriguez JA, Jiménez A, Borreguero-Léon JM, Belmonte F, Medina JC, LLiminana MC, Ferrer-Agüero JM, Ferreres J, Mora ML, Lubillo S, Sánchez M, Barrios Y, Sierra A, Páramo JA: Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metal-loproteinases-1 blood levels as biomarkers of severity and mortality in sepsis. Crit Care 2009, 13: R158. 10.1186/cc8115PubMedCentralCrossRefPubMed Lorente L, Martin MM, Labarta L, Diaz C, Solé-Violán J, Blanquer J, Orbe J, Rodriguez JA, Jiménez A, Borreguero-Léon JM, Belmonte F, Medina JC, LLiminana MC, Ferrer-Agüero JM, Ferreres J, Mora ML, Lubillo S, Sánchez M, Barrios Y, Sierra A, Páramo JA: Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metal-loproteinases-1 blood levels as biomarkers of severity and mortality in sepsis. Crit Care 2009, 13: R158. 10.1186/cc8115PubMedCentralCrossRefPubMed
2.
go back to reference Opdenakker G, Steen PHE, Van Damme J: Gelatinase B: a tuner and amplifier of immune functions. Trends Immunol 2001, 22: 571-579. 10.1016/S1471-4906(01)02023-3CrossRefPubMed Opdenakker G, Steen PHE, Van Damme J: Gelatinase B: a tuner and amplifier of immune functions. Trends Immunol 2001, 22: 571-579. 10.1016/S1471-4906(01)02023-3CrossRefPubMed
3.
go back to reference Elkington PTG, O'Kane CM, Friedland JS: The paradox of matrix metalloproteinases in infectious disease. Clin Exp Immunol 2005, 142: 12-20. 10.1111/j.1365-2249.2005.02840.xPubMedCentralCrossRefPubMed Elkington PTG, O'Kane CM, Friedland JS: The paradox of matrix metalloproteinases in infectious disease. Clin Exp Immunol 2005, 142: 12-20. 10.1111/j.1365-2249.2005.02840.xPubMedCentralCrossRefPubMed
4.
go back to reference Pugin J, Widmer MC, Kossodo S, Liang CM, Preas HL II, Suffredini AF: Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators. Am J Respir Cell Mol Biol 1999, 20: 458-464.CrossRefPubMed Pugin J, Widmer MC, Kossodo S, Liang CM, Preas HL II, Suffredini AF: Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators. Am J Respir Cell Mol Biol 1999, 20: 458-464.CrossRefPubMed
5.
go back to reference Chromek M, Tullus K, Lundahl J, Brauner A: Tissue inhibitor of metalloproteinase 1 activates normal human granulocytes, protects them from apoptosis, and blocks their transmigration during inflammation. Infect Immun 2004, 72: 82-88. 10.1128/IAI.72.1.82-88.2004PubMedCentralCrossRefPubMed Chromek M, Tullus K, Lundahl J, Brauner A: Tissue inhibitor of metalloproteinase 1 activates normal human granulocytes, protects them from apoptosis, and blocks their transmigration during inflammation. Infect Immun 2004, 72: 82-88. 10.1128/IAI.72.1.82-88.2004PubMedCentralCrossRefPubMed
6.
go back to reference Kotyza J, Pesek M, Puzman P, Havel D: Progelatinase B/matrix metalloproteinase-9 proenzyme as a marker of pleural inflammation. Exp Lung Res 2004, 30: 297-309. 10.1080/01902140490276393CrossRefPubMed Kotyza J, Pesek M, Puzman P, Havel D: Progelatinase B/matrix metalloproteinase-9 proenzyme as a marker of pleural inflammation. Exp Lung Res 2004, 30: 297-309. 10.1080/01902140490276393CrossRefPubMed
7.
go back to reference Ferroni P, Basili S, Martini F, Cardarello CM, Ceci F, Di Franco M, Bertazzoni G, Gazzaniga PP, Alessandri C: Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker for inflammation. J Investig Med 2003, 51: 295-300. 10.2310/6650.2003.3563PubMed Ferroni P, Basili S, Martini F, Cardarello CM, Ceci F, Di Franco M, Bertazzoni G, Gazzaniga PP, Alessandri C: Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker for inflammation. J Investig Med 2003, 51: 295-300. 10.2310/6650.2003.3563PubMed
8.
go back to reference Yassen KA, Galley HF, Webster NR: Matrix metalloproteinase-9 concentrations in critically ill patients. Anaesthesia 2001, 56: 729-732. 10.1046/j.1365-2044.2001.02083.xCrossRefPubMed Yassen KA, Galley HF, Webster NR: Matrix metalloproteinase-9 concentrations in critically ill patients. Anaesthesia 2001, 56: 729-732. 10.1046/j.1365-2044.2001.02083.xCrossRefPubMed
9.
go back to reference Hoffmann U, Bertsch T, Dvortsak E, Liebetrau C, Lang S, Liebe V, Huhle G, Borggrefe M, Brueckmann M: Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP-1 in severe sepsis. Scand J Infect Dis 2006, 38: 867-872. 10.1080/00365540600702058CrossRefPubMed Hoffmann U, Bertsch T, Dvortsak E, Liebetrau C, Lang S, Liebe V, Huhle G, Borggrefe M, Brueckmann M: Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP-1 in severe sepsis. Scand J Infect Dis 2006, 38: 867-872. 10.1080/00365540600702058CrossRefPubMed
10.
go back to reference Nakamura T, Ebihara I, Shimada N, Shoji H, Koide H: Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment. Am J Med Sci 1998, 316: 355-360. 10.1097/00000441-199812000-00001CrossRefPubMed Nakamura T, Ebihara I, Shimada N, Shoji H, Koide H: Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment. Am J Med Sci 1998, 316: 355-360. 10.1097/00000441-199812000-00001CrossRefPubMed
11.
go back to reference Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, Vadas L, Pugin J: Diagnostic value of procalcitonin, interleukin-6 and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001, 164: 396-402.CrossRefPubMed Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, Vadas L, Pugin J: Diagnostic value of procalcitonin, interleukin-6 and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001, 164: 396-402.CrossRefPubMed
12.
go back to reference Castelli GP, Prognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L: Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care 2004, 8: R234-R240. 10.1186/cc2877PubMedCentralCrossRefPubMed Castelli GP, Prognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L: Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care 2004, 8: R234-R240. 10.1186/cc2877PubMedCentralCrossRefPubMed
13.
go back to reference Clech C, Ferriere F, Karoubi P, Fosse JP, Cupa M, Hoang P, Cohen Y: Diagnostic and prognostic value of procalcitonin in patients with septic shock. Crit Care Med 2004, 32: 1166-1169. 10.1097/01.CCM.0000126263.00551.06CrossRef Clech C, Ferriere F, Karoubi P, Fosse JP, Cupa M, Hoang P, Cohen Y: Diagnostic and prognostic value of procalcitonin in patients with septic shock. Crit Care Med 2004, 32: 1166-1169. 10.1097/01.CCM.0000126263.00551.06CrossRef
14.
go back to reference Roch A, Allardet-Servent J, Michelet P, Oddoze C, Forel JM, Barrau K, Loundou A, Perrin G, Auffray JP, Portugal H, Papazian L: NH 2 terminal pro-brain natriuretic peptide plasma level as an early marker of prognosis and cardiac dysfunction in septic shock patients. Crit Care Med 2005, 33: 1001-1007. 10.1097/01.CCM.0000162561.82012.E9CrossRefPubMed Roch A, Allardet-Servent J, Michelet P, Oddoze C, Forel JM, Barrau K, Loundou A, Perrin G, Auffray JP, Portugal H, Papazian L: NH 2 terminal pro-brain natriuretic peptide plasma level as an early marker of prognosis and cardiac dysfunction in septic shock patients. Crit Care Med 2005, 33: 1001-1007. 10.1097/01.CCM.0000162561.82012.E9CrossRefPubMed
15.
go back to reference Gibot S, Pe LR, Bollaert PE, Kolopp-Sarda MN, Béné MC, Faure GC, Lévy B: Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock. Intensive Care Med 2005, 31: 594-597. 10.1007/s00134-005-2572-xCrossRefPubMed Gibot S, Pe LR, Bollaert PE, Kolopp-Sarda MN, Béné MC, Faure GC, Lévy B: Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock. Intensive Care Med 2005, 31: 594-597. 10.1007/s00134-005-2572-xCrossRefPubMed
16.
go back to reference Lalu MM, Gao CQ, Schulz R: Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac dysfunction: a potential role for MMP-9. Mol Cell Biochem 2003, 251: 61-66. 10.1023/A:1025417529167CrossRefPubMed Lalu MM, Gao CQ, Schulz R: Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac dysfunction: a potential role for MMP-9. Mol Cell Biochem 2003, 251: 61-66. 10.1023/A:1025417529167CrossRefPubMed
Metadata
Title
Matrix metalloproteinases and their inhibitors: promising novel biomarkers in severe sepsis?
Authors
Ursula Hoffmann
Martina Brueckmann
Martin Borggrefe
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2009
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc8156

Other articles of this Issue 6/2009

Critical Care 6/2009 Go to the issue