Table 2. Effects of caspase-, MLKL- and RIPK3-deficient mice in sepsis.

	Outcomes in sepsis
Knockout strains	Protective	Non-protective/deleterious
Caspase-1	Improves survival; attenuates IL-1β production; decreases lymphocyte apoptosis.40	Higher mortality in Salmonella typhimurium infection.63 Not protective against TNF-α-induced SIRS.53
Caspase-3	Improves survival; less T- and B-cell apoptosis.9	No effect on survival in LPS-induced sepsis.39, 42 Does not improve survival against lethal dose of TNF-α.53
Caspase-7	Protects from LPS-induced lethality independently of the excessive production of serum cytokines; resistant to lymphocyte apoptosis.39	Not protective against lethal dose of LPS challenges.41 No survival benefit against TNF-α-induced SIRS.53
Caspase-11	Survival benefits; critical for caspase-1 activation; defects in IL-1β and IL-18 production.44	Partially protective against a lethal dose of TNF-α.41
Caspase-1/11 double KO	Improves survival; defects in IL-1β and IL-18 production.44	Partly improves survival against a lethal dose of TNF-α.41
Caspase-3/11 double KO	Significantly improves survival.71
IL-1β/IL-18 double KO	Exerts potential survival benefits against LPS/TNF-α/CLP-induced sepsis.41
IL-1β/IL-18/caspase-7 triple KO		No additional benefit in improving survival as compared with the IL-1β/IL-18 double KO.41
Caspase-12	Improves survival; Enhanced clearance of pathogens; Maintains IL-1β production.49
MLKL	Blocks TNF-α-driven necroptosis.91	No effect on improving septic shock-induced animal death.18
RIPK3	Decreases cellular necroptosis; protects mice from TNF-induced SIRS; improves survival in CLP-induced sepsis.53	Does not protect from polymicrobial sepsis-induced mortality.18

Abbreviations: IL-1β, interleukin-1 beta; KO, knockout; MLKL, mixed lineage kinase domain-like protein; RIPK3, receptor-interacting serine–threonine kinase 3; SIRS, systemic inflammatory response syndrome; TNF-α, tumor necrosis factor alpha