Table 1. Sepsis biomarkers.

Marker		Function	Clinical relevance	Ref.
Soluble
	Lactate	Byproduct of glucose metabolism, produced from pyruvate during anaerobic metabolism	• Hyperlactatemia indicative of cell hypoxia states when aerobic is converted to anaerobic metabolism	(30,31)
			• Also elevated with reduced lactate clearance from sepsis-induced liver dysfunction
			• Also elevated with excess glycolysis, thiamine deficiency, and other conditions, therefore non-specific
	Blood pH	Indicative of metabolic acidosis, a result of increased anion production	• Acidified blood correlates with a decrease in tissue perfusion and contributes to reduced cardiac contractility, ATP generation, and negatively impacts the immune response	(32,33)
			• Can be a result of other disease states, and not specific to sepsis
	CRP	Binds to pathogens and dying cells to facilitate enhanced phagocytosis and clearance	• Produced by the liver at early phases of sepsis in response to bacterial infection, but also as a response to many other inflammatory stimuli	(34,35,36)
	PCT	Prohormone of calcitonin secreted in response to bacterial stimulation	• PCT concentrations above 0.1 ng/mL indicative of bacterial infection	(36,37)
			• Half-life is relatively short, and concentrations can normalize quickly
	HMGB-1	HMGB-1 protein binds to DNA and creates a scaffold for chromatin formation	• Alarmin released from cells under stress	(38,39)
			• During sepsis, can bind inflammatory mediators such as RAGE and TLRs
			• Higher levels in the blood indicative of inflammation, however not specific to sepsis
Cell surface
	CD64	High affinity Fc-g-receptor, highly expressed on macrophages and eosinophils, binds to immunoglobulins and mediates clearance of antibody coated cells	• Expressed on neutrophils only during sepsis, specifically during bacterial infections	(36,40)
	VLA-3 (a3b1)	Member of the integrin family, mediates adhesion of immune cells to fibronectin and collagen in extracellular matrices during cell migration	• Upregulated on hyperinflammatory neutrophils exclusively during sepsis, distinguishing from sterile inflammation or SIRS	(26,41,42)
	CCR2	Chemokine receptor 2, expressed on monocytes and some macrophages to facilitate chemotaxis and regulation of tissue specific immune cell homing	• Higher expression levels during sepsis indicative of pro-inflammatory monocyte egress from bone marrow and subsequent infiltration into inflamed tissues	(23,43,44,45)
	CX3CR1	Fractalkine receptor, highly expressed on tissue-resident macrophages, facilitates leukocyte adhesion and migration during steady state	• Expressed on monocytes during immunosuppressive phases of sepsis	(22,25,46,47,48)

SIRS, systemic inflammatory response syndrome; HMGB-1, high mobility group protein B1; RAGE, receptor for advanced glycation end products.