Vizelet orosomucoid, mint gyulladásos biomarker szepszisben

Abstract

The leading causes of global morbidity and mortality (cardiovascular diseases, malignancies and infections) are all associated with activation of the inflammatory system. Systemic inflammation often results in severe complications. From these disorders, sepsis has to be highlighted, which has been known since the ancient times, however it still remains a challenging healthcare problem with relevant social and economic burden. Sepsis with an approximately 30% mortality rate and high costs of care is one of the most serious conditions of intensive care unit (ICU) admissions. Sepsis is a heterogeneous, complex clinical syndrome with various etiology, severity and prognosis. Early recognition of sepsis and distinguishing it from systemic inflammatory response syndrome (SIRS) is essential to improve disease outcome. Microbiological and laboratory tests provide a considerable help in the diagnosis. Certain biomarkers might be capable of prognostication, recognition of organ dysfunction and guiding antibiotic therapy as well. In the past few decades approximately 200 sepsis markers have been studied. Most of the biomarkers belong to the mediators of inflammatory response. The latest diagnostic guidelines regarding sepsis dedicated serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hsCRP) measurements if sepsis is suspected, even if these markers also possess some limitations. It is particularly advantageous, if a marker can be measured from a non-invasively obtained sample and if it is suitable for real-time monitoring of the inflammatory activation. Recently urinary proteomics also revealed the importance of several urinary proteins in systemic and in local processes as well. Orosomucoid (ORM) or α-1-acid glycoprotein is a major positive acute phase protein. Although ORM has been described in 1950, and numerous function of ORM has already been explored, its exact biologic role is not well clarified. ORM is an extensively glycosylated 41–43 kDa glycoprotein with extraordinary structure yielding unique features and functions. As a member of the immunocalin protein family, ORM plays a role in transporting biomolecules and drugs influencing their pharmacokinetics and takes part in the regulation of inflammatory processes with anti-inflammatory and immunomodulating activities. In vitro studies showed that ORM has several effects on all major leukocyte types: it inhibits lymphocyte proliferation, neutrophil chemotaxis, superoxide generation and platelet aggregation, as well. Animal experiments confirmed that ORM improves the outcome from different types of shock, sepsis, and it is important in maintaining perfusion of vital organs, and regulating capillary permeability.