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