Blanquer, J. (José)

Lorente, L. (Leonardo)

Martin, M.M. (María M.)

Paramo, J.A. (José Antonio)

Sole-Violan, J. (Jordi)

Dadun, University of Navarra

We read with interest the commentary by Hoﬀ mann and colleagues [1] on our manuscript recently published in Critical Care showing that matrix metalloproteinase (MMP)-9, MMP-10 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 could be new biomarkers of severity and mortality in sepsis [2]. As they stated, the lack of serial measurements of MMPs and TIMPs over clinical evolution was as a limitation of our study. Despite this limitation, our results suggest that MMPs and TIMPs may be of pathophysiological signiﬁ cance in sepsis.Some clinical studies have found higher circulating levels of MMP-9 [2-4] and TIMP-1 [2,3] in septic patients than in healthy controls, and higher levels of TIMP-1 [2,3] or MMP-9 [4] in nonsurviving than in surviving septic patients. Our study also reports, for the ﬁ rst time, that MMP-10 circulating levels are also elevated in septic patients [2]. According to the results of some in vitrostudies, MMP-10 could play a role in infection, since increased MMP-10 gene transcription was observed after infective stimulation of human and mice cells.On the other hand, we think the correlation between MMP-9, TIMP-1 and markers of coagulopathy, and the lower MMP-9/TIMP-1 ratio in nonsurviving than in surviv ing septic patients found in our study, may be associated with a higher prothrombotic/antiﬁ brinolytic state, responsible for the capillary thrombosis, multiple organ dysfunction, and death.Finally, from a therapeutic perspective, the develop-ment of modulators of MMP/TIMP activity could be used as a new class of drugs for the treatment of severe sepsis [5].AbbreviationsMMP = matrix metalloproteinase; TIMP = tissue inhibitor of matrix metalloproteinases.AcknowledgementsThe present study was supported, in part, by a grant from the Canary Islands Foundation for Health and Research (FUNCIS number PI 42/07) (Tenerife, Spain), by a grant from the Working Group on Infectious Diseases of the Spanish Society of Intensive Medicine, Critical Care, and Coronary Units (GTEI-SEMICYUC-2009), by funding from the Rafael Clavijo Foundation for Biomedical Research (Tenerife, Spain) and by the UTE project CIMA (University of Navarra, Spain).Author details1Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n. La Cuesta, La Laguna 38320, Santa Cruz de Tenerife, Spain2Intensive Care Unit. Hospital Universitario Nuestra Señora de Candelaria. Crta del Rosario s/n. Santa Cruz de Tenerife - 38010. Spain3Intensive Care Unit. Hospital Universitario Dr. Negrín. Barranco de la Ballena s/n. Las Palmas de Gran Canaria - 35010. Spain4Intensive Care Unit. Hospital Clínico Universitario de Valencia. Avda. Blasco Ibáñez nº17-19. Valencia - 46004. Spain5Atherosclerosis Research Laboratory. CIMA-University of Navarra. Avda Pío XII nº55. Pamplona - 31008. SpainCompeting interestsThe authors declare that they have no competing interests.Published: 19 January 2010References1. Hoff mann U, Brueckmann M, Borggrefe M: Matrix metalloproteinases and their inhibitors: promising novel biomarkers in severe sepsis? Crit Care 2009, 13:1006.2. Lorente L, Martin MM, Labarta L, Diaz C, Sole-Violan J, Blanquer J, Orbe J, Rodriguez JA, Jimenez A, Borreguero-Leon JM, Belmonte F, Medina JC, Lliminana MC, Ferrer-Aguero JM, Ferreres J, Mora ML, Lubillo S, Sanchez M, Barrios Y, Sierra A, Paramo JA: Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis. Crit Care 2009, 13:R158.3. Hoff mann 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 2006, 38:867-872.4. 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: eff ect of fi ber-immobilized polymyxin B treatment. Am J Med Sci 1998, 316:355-360.5. Zhu S, Ashok M, Li J, Li W, Yang H, Wang P, Tracey KJ, Sama AE, Wang H: Spermine protects mice against lethal sepsis partly by attenuating surrogate infl ammatory markers. Mol Med 2009, 15:275-282.© 2010 BioMed Central LtdMatrix metalloproteinases and their inhibitors as biomarkers of severity in sepsisLeonardo Lorente*1, María M Martín2, Jordi Solé-Violán3, José Blanquer4 and José Antonio Páramo5See related commentary by Hoff mann et al., http://ccforum.com/content/13/6/1006LETTER*Correspondence: lorentemartin@msn.com1Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n. La Cuesta, La Laguna 38320, Santa Cruz de Tenerife, SpainFull list of author information is available at the end of the articleLorente et al. Critical Care 2010, 14:402 http://ccforum.com/content/14/1/402doi:10.1186/cc8211Cite this article as: Lorente L, et al.: Matrix metalloproteinases and their inhibitors as biomarkers of severity in sepsis. Critical Care 2010, 14:402.© 2010 BioMed Central Ltd

Matrix metalloproteinases and their inhibitors as biomarkers of severity in sepsis

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