TIMP-1 as a biomarker in the ICU

In the previous issue of Critical Care, the Spanish group of Lorente and colleagues reports results in which the role of the 372 T/C polymorphism of tissue inhibitor of metalloproteinase (TIMP)-1 (rs 4898) and serum levels of TIMP-1 were related to the outcome of 275 patients with severe sepsis [1]. Th ey found the T-allele in the 372 T/C genetic poly morphism of TIMP-1 and increased levels of TIMP-1 to be associated with lower survival rates, and suggest that this genetic polymorphism may have prognostic impli cations in severe septic patients. Sepsis represents a systemic infl ammatory response to an infectious agent and may lead to multiple organ failure, increased mortality and costs. Genetic testing has been discussed as a strategy to identify septic patients with a poor prognosis. Advances in genetic sequence analysis and high-throughput platform analysis of gene expression improved the understanding of immunopathogenetics during sepsis [2]. TIMPs naturally occur as inhibitors of matrix metalloproteinases (MMPs), whilst additionally revealing growth factor functions [3]. TIMP-1 itself inhibits almost all of the diff erent MMP subtypes [3]. TIMP-1 activates human granulocytes, protecting them from apoptosis and blocking their transmigration during infl ammation [4]. Several studies showed increased protein levels of MMPs and TIMPs, and evaluated the prognostic value of TIMP-1 in patients with severe sepsis [5,6]. Increasing evidence suggests that diff erences of a specifi c disease manifestation and outcome may result from the patient’s individual genetic disposition. A study by Skarmoutsou and colleagues demonstrated the prognostic impact of the 372 T/C TIMP-1 genetic polymorphism for the onset of systemic sclerosis in women [7]. An association of genetic polymorphisms of the X-linked TIMP-1 gene with the risk of developing certain other diseases has been reported, the 372 T/C TIMP-1 polymorphism being the most studied variant [7-9].