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Table 1 Preclinical evidence that suggests preventing immune cell apoptosis or improving immune cell survival has a positive impact on sepsis mortality rates

From: Role of the adaptive immune response in sepsis

Model Intervention Effect on immune system Effect in model
Cecal ligation and puncture (CLP) in C3H-HeJ Mice [83] Overexpression of Bcl-2 on T-lymphocytes -Protected from sepsis-induced T-lymphocyte apoptosis in thymus and spleen
-Decreased splenic B cell apoptosis
-Improved animal survival
-Decreased bacterial burden
CLP in ND4 mice [84] Selective caspase-3 inhibition or polycaspase inhibition via small molecule inhibitor -Prevented lymphocyte apoptosis -Decreased bacteraemia
-Improved survival
CLP in C57BL/6 [43] Anti-PD-L1 antibody -Prevented sepsis-induced lymphocyte apoptosis
-Increased TNF-α and IL-6 production
-Decreased IL-10 production
-Enhanced bacterial clearance
-Improved survival
CLP in mice [41] Knockout of PD-1 -Resistance to sepsis-induced cellular dysfunction
-Suppressed inflammatory cytokine response
-Decreased bacterial burden
-Improved survival
CLP in CD1 mice [42] Anti-PD-L1 antibody -Prevented sepsis-induced immune-depletion of lymphocytes and DCs by blocking apoptosis -Increased Bcl-XL
-Improved survival
CLP in CD-1 or C57/BL6 mice [85] Anti-CTLA4 antibody -Reduced sepsis-induced apoptosis -Improved survival at low doses
CLP in C57BL/6 mice [86] Intra-thymic injections of recombinant adenovirus construct expressing human IL-10 Reduced thymocyte apoptosis -Increased Bcl-2 expression
-Reduced caspase-3 activity
-Reduced bacteraemia
-Increased survival
CLP or Pseudomonas aeruginosa pneumonia in CD-1 mice [87] Recombinant IL-15 -Blocked sepsis-induced apoptosis of NK cells, DCs and CD8+ T cells
-Increased circulating NK cell production of IFN-γ
-Increased anti-apoptotic Bcl-2
-Decreased pro-apoptotic Bim and PUMA
-Increased survival
CLP in C57BL6 or CD1 mice [88] Recombinant human IL-7 -Improved the delayed type hypersensitivity response
-Increased absolute splenic counts, proliferation and activation of CD4 and CD8 T cells
-Increased expression of the adhesion molecule leukocyte function–associated antigen-1
-Reversed T cell defect in cytokine production
-Improved survival
-Decreased tissue fungal colony counts in liver
CLP in C57BL6 or CD1 mice [89] Recombinant human IL-7 -Blocked apoptosis of CD4 and CD8 T cells
-Restored IFN-γ production
-Improved effector cell recruitment to infected site
-Prevented loss of delayed hypersensitivity
-Increased expression of leukocyte adhesion molecules LFA-1 and VLA-4
-Increased Bcl-2
-Improved survival