Immunomodulation in Sepsis: The Role of Endotoxin Removal by Polymyxin B-Immobilized Cartridge

Table 2

Summary of mechanisms described for polymyxin B-immobilized cartridge hemoperfusion.

Molecules	Description	Effect; of PMX	Clinical features after PMX	References
Endotoxin	Component of the external membrane of gram-negative microorganisms, recognized by immune cells	↓	Interruption of inflammatory cascade	[52–55, 58, 59, 62–64]
IL-1; IL-6; IL-8; IL-9; IL-10; IL-12; IL-17; αTNF	Pro- and anti-inflammatory cytokines; their overproduction is deleterious in sepsis	↓	Decrease in the excessive systemic host inflammatory response to infection	[54, 61, 63, 68–70, 72, 88]
Plasminogen activator inhibitor (PAI-1)	Component of the coagulation system that downregulates fibrinolysis in the circulation, favoring coagulation	↓	Regulation of fibrinolysis and reversal of the occurrence of sepsis-associated thrombosis	[54, 55, 61]
Neutrophil elastase	Protease that hydrolyzes lung elastase and other proteins	↓	Reduction of pulmonary tissue destruction	[61, 71]
High mobility group box protein 1,; HMGB-1; receptor for advanced glycation end-products (RAGE), S100A12	HMBG-1 is a cytokine to trigger inflammatory mediators; RAGE is a receptor involved in HMBG-1 signaling; S100A12 is a mediator involved in acute lung injury	↓	Decrease in the excessive systemic host inflammatory response to infection	[63, 74, 102]
Anandamide	Intrinsic cannabinoid that induces hypotension in septic shock	↓	Decrease in septic shock-associated hypotension	[78]
Nitric oxide	Produces vasodilatation and hypotension	↓	Decrease in septic shock-associated hypotension	[79]
Erythropoietin	Protein that controls red blood cells production, elevated in sepsis	↓	Prognostic biomarker in sepsis	[70]
Troponin T	Protein found in cardiac muscle	↓	Decrease in myocardial cell damage	[80]
Angiopoietin-1 and -2	Angiopoietin-1 reduces pulmonary inflammation and permeability. Angiopoietin-2 interferes with angiopoietin-1, resulting in pulmonary inflammation and increased permeability	Balance	Decrease in acute lung injury	[75]
Vascular endothelial growth factor (VEGF)	Growth factor involved in several acute and chronic lung diseases	↓	Improvement of lung function	[69]
Monocytes, neutrophils, and lymphocytes	Immune cells involved in inflammatory response	↓	Decrease in the interaction between monocytes and functionally associated cells, decreasing inflammatory response, and decrease in neutrophil and lymphocyte response	[82, 83]
Platelet activator factors (PAF) (P-selectin, β-Thromboglobulin, Platelet factor 4)	PAF stimulates platelets, increasing procoagulation status in sepsis	↓	Decrease inprothrombotic status	[52]
HLA-DR and CD16 expression monocytes on granulocytes	Surface antigen expressions HLA-DR and CD-16 are decreased in sepsis	↑	Increasing in surface antigen expression on immune cells helps the recovery from immunoparalysis in sepsis	[56]
CD4+CD25+Foxp3+ Treg	T-lymphocytes, responsible formaintaining immunological homeostasis and tolerance, are increased in sepsis	↓	Recovery from immunoparalysis in sepsis	[88]
Apoptotic factors (Fas- and caspase-mediated)	Factors that activate cell programmed death of tubular cells	↓	Improvement in renal function by reduction of proapoptotic factors	[94]
Metalloproteinase MMP9	Protease involved in degradation of the basement membrane associated with the alveolar epithelium	↓	Decrease in alveolar destruction and improvement in respiratory function	[62, 101]

IL: interleukin; PMX: polymyxin-B immobilized cartridge.