Table 2.
Cell death–mediated inflammatory cytokine-driven diseases
DiseaseKey regulatorTreatment targetReference
Behcet’s disease IL-1
IL-18? 
IL-1R (anakinra)
IL-1β (canakinumab) 
Masters, 2013; Vitale et al., 2016  
Sweet’s syndrome (including neutrophilic dermatoses) PTPN6?
RIPK1
IL-1α
MLKL? 
IL-1α?
GSDMD?
MLKL?
 
Nesterovitch et al., 2011; Lukens et al., 2013  
Schnitzler syndrome IL-1β IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy receptor (rilonacept) 
de Koning et al., 2015  
AOSD IL-1β
IL-18?
 
IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy receptor (rilonacept) 

Lee et al., 2015; Junge et al., 2017  
JIA/soJIA IL-1 IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy (rilonacept) 
Pascual et al., 2005; Cimaz, 2016  
HLH IL-1?
IL-18? 
IL-1R (anakinra)?
IL-18? 
Schulert and Grom, 2015  
Osteomyelitis IL-1β
NLRP3
Caspase-8
MLKL? 
IL-1R (anakinra)?
MLKL? 
Lukens et al., 2014; Gurung et al., 2016a  
Lung cancer IL-1β IL-1β (canakinumab) Ridker et al., 2017b  
Cardiovascular diseases IL-1α?, IL-1β IL-1β (canakinumab) Ridker et al., 2017a  
Gout NLRP3
MSU crystals
IL-1
GSDMD
MLKL? 
IL-1R (anakinra)?
IL-1β (canakinumab)?
IL-1 decoy (rilonacept)? 
Dayer et al., 2017  
Kidney diseases IL-18
IL-1β
RIPK3
MLKL?
GSDMD? 
IL-18?
MLKL (necrosulfonamide)?
GSDMD? 
Wu et al., 2008; Chen et al., 2018a; Sarhan et al., 2018b  
Alzheimer’s disease NLRP3
ASC 
NLRP3 (MCC950)?
ASC?
GSDMD? 
Venegas et al., 2017  
Ischemic brain injury NLRP3
NLRC4?
GSDMD
RIPK1
RIPK3?
MLKL? 
RIPK1 (Necrostatin-1)
RIPK3 (GSK-872) 
Degterev et al., 2005; Chen et al., 2018b; Xu et al., 2018b; Poh et al., 2019; Zhang et al., 2019  
Rheumatoid arthritis TNF
IL-1?
GSDMD?
MLKL? 
TNF Yamanaka, 2015; Dayer et al., 2017  
Septic shock Caspase-11
GSDMD
Caspase-8 
GSDMD? Kayagaki et al., 2015; Kang et al., 2018; Mandal et al., 2018  
Inflammatory bowel diseases MLKL?
NLRP3
IL-1α 
NLRP3 (MCC950)?
IL-1α (MABp1)?
MLKL (necrosulfonamide)? 
Malik et al., 2016; Li et al., 2018  
DiseaseKey regulatorTreatment targetReference
Behcet’s disease IL-1
IL-18? 
IL-1R (anakinra)
IL-1β (canakinumab) 
Masters, 2013; Vitale et al., 2016  
Sweet’s syndrome (including neutrophilic dermatoses) PTPN6?
RIPK1
IL-1α
MLKL? 
IL-1α?
GSDMD?
MLKL?
 
Nesterovitch et al., 2011; Lukens et al., 2013  
Schnitzler syndrome IL-1β IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy receptor (rilonacept) 
de Koning et al., 2015  
AOSD IL-1β
IL-18?
 
IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy receptor (rilonacept) 

Lee et al., 2015; Junge et al., 2017  
JIA/soJIA IL-1 IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy (rilonacept) 
Pascual et al., 2005; Cimaz, 2016  
HLH IL-1?
IL-18? 
IL-1R (anakinra)?
IL-18? 
Schulert and Grom, 2015  
Osteomyelitis IL-1β
NLRP3
Caspase-8
MLKL? 
IL-1R (anakinra)?
MLKL? 
Lukens et al., 2014; Gurung et al., 2016a  
Lung cancer IL-1β IL-1β (canakinumab) Ridker et al., 2017b  
Cardiovascular diseases IL-1α?, IL-1β IL-1β (canakinumab) Ridker et al., 2017a  
Gout NLRP3
MSU crystals
IL-1
GSDMD
MLKL? 
IL-1R (anakinra)?
IL-1β (canakinumab)?
IL-1 decoy (rilonacept)? 
Dayer et al., 2017  
Kidney diseases IL-18
IL-1β
RIPK3
MLKL?
GSDMD? 
IL-18?
MLKL (necrosulfonamide)?
GSDMD? 
Wu et al., 2008; Chen et al., 2018a; Sarhan et al., 2018b  
Alzheimer’s disease NLRP3
ASC 
NLRP3 (MCC950)?
ASC?
GSDMD? 
Venegas et al., 2017  
Ischemic brain injury NLRP3
NLRC4?
GSDMD
RIPK1
RIPK3?
MLKL? 
RIPK1 (Necrostatin-1)
RIPK3 (GSK-872) 
Degterev et al., 2005; Chen et al., 2018b; Xu et al., 2018b; Poh et al., 2019; Zhang et al., 2019  
Rheumatoid arthritis TNF
IL-1?
GSDMD?
MLKL? 
TNF Yamanaka, 2015; Dayer et al., 2017  
Septic shock Caspase-11
GSDMD
Caspase-8 
GSDMD? Kayagaki et al., 2015; Kang et al., 2018; Mandal et al., 2018  
Inflammatory bowel diseases MLKL?
NLRP3
IL-1α 
NLRP3 (MCC950)?
IL-1α (MABp1)?
MLKL (necrosulfonamide)? 
Malik et al., 2016; Li et al., 2018  

AOSD, adult-onset Still’s disease; HLH, hemophagocytic lympho-histiocytosis; JIA, juvenile idiopathic arthritis; soJIA, systemic-onset juvenile idiopathic arthritis.

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