ABSTRACT
90Sepsis is a serious medical condition caused by a severe systemic infection leading to a systemic inflammatory response. The more critical subsets of sepsis include severe sepsis (sepsis with organ dysfunction) and septic shock (sepsis with refractory arterial hypotension). It is characterized by a systemic over-reaction of the inflammatory and the coagulatory system resulting from an infection, which can quickly lead to multiple organ failure and death.
It is known that the host response to Gram-negative bacterial LPS— an important component of sepsis pathology involves its interaction with Toll-like receptors (TLRs) and cluster differentiation 14 (CD14) receptors present on the monocytes and macrophages which initiate the production of proinflammatory mediators such as interleukin (IL-6), interleukin (IL-8), and tumor necrosis factor (TNF-α). LPS also induces the production of acute phase response proteins by the liver. Serum procalcitonin is currently the only USFDA (US Food and Drug Administration) approved biomarker for the diagnosis and monitoring of the progression of sepsis, though other acute phase reactants like CRP (C reactive protein) and Serum amyloid A protein are also in use. The diagnosis of sepsis and evaluation of its severity is complicated by the highly variable and nonspecific nature of the signs and symptoms of sepsis. Recently, genes involved in innate immune recognition have gained attention. In particular, variation in the genes encoding the so-called TLRs, Mannose-Binding Lectin (MBL), activated protein C (APC), etc., have been extensively studied. Although these studies have helped in devising methods for treatment, yet the incidence of sepsis is rising. Very little is known about the genetic susceptibility of an individual; the risk of sepsis increases because of the various immunosuppressive procedures given to patients like drugs, chemotherapy, radiotherapy, etc. Recently identified biomarkers slouable triggering receptor expressed on myeloid cells (sTREM), soluable form of urokinase type plasminogen receptor (suPAR), Nociceptin, Presepsin have shown significant results in the diagnosis of sepsis and further understanding on how they correlate with sepsis outcome can prove their potential as novel biomarkers. In this review, a panorama of sepsis biomarkers identified till date, their role in therapy, and the latest developments in the understanding of sepsis will be discussed.
