From: Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis
Author, year | Exp ID | Checkpoint molecule target | Infection organism | Infection site | Summary of the effect of checkpoint inhibitor treatment compared to control treatment | |||
---|---|---|---|---|---|---|---|---|
Serum cytokines | Other cytokines | Cell populations | Apoptosis | |||||
Seo, 2008 | 1 | PD-L1 | L. mono | IV | NR | Heat-killed LM-stim splenocyte TNFα, IL-12p40 and NO production and NK cell IFNγ production decreased on D+3^ | Spleen LM-specific CD8s and IFNγ+ CD8s decreased on D+7 and +25^ | Frequency of annexin V+ CD8s unchanged at 6 or 24 h |
Brahmamdam, 2010 | 1 | PD-1 | CLP | IP | IL-6, IL-10, TNFα, IFNγ not different on D+1ns | CD3/CD28 stim splenocyte IL-6 production increased on D+2^ but IL-10, TNFα, and IFNγ not differentns | Total splenocytes, CD4, CD8, B cells, NK cells, and DCs increased on D+2^^ | Splenic CD3 apoptosis decreased on D+2^^ |
Zhang, 2010* | 1 | PD-L1 | CLP | IP | NR | NR | NR | NR |
2 | PD-L1 | CLP | IP | TNFα and IL-6 increased, IL-10 decreased on D+1^ | NR | Total cell numbers, CD3, and CD19 cell numbers increased on D+1 in blood, spleen, and thymus^ | Splenic and thymus lymphocyte apoptosis decreased on D+1^ | |
Inoue, 2011** | 1 | CTLA-4 | CLP | IP | TNFα, IL-6, IL-10, IFNγ not different on D+2ns | CD3/CD28 stim splenocyte IL-6, IL-10, TNFα, IFNγ production not different on D+2ns | Total splenocyte, CD4, and CD8 numbers unchanged at D+7ns. Naïve, effector memory and central memory CD4 and CD8 unchanged at D+7ns | Splenic CD4 and CD8 apoptosis decreased on D+2^ |
2 | CTLA-4 | CLP | IP | NR | NR | NR | NR | |
3 | CTLA-4 | CLP | IP | NR | NR | NR | NR | |
4 | CTLA-4 | CLP (C.a. D+4)## | IP and IV | NR | NR | NR | NR | |
Kobayashi, 2013 | 1 | BTLA | LPS | IV | NR | NR | NR | NR |
Chang, 2013 | 1 | PD-1 | CLP (C.a. D+3)## | IP and IV | NR | CD3/CD28 stim splenocyte IFNγ production increased on D+9^ | Macrophage and DC MHCII expression increased at D+9^ | NR |
2 | PD-L1 | CLP (C.a. D+3)## | IP and IV | NR | CD3/CD28 stim splenocyte IFNγ production not different on D+9ns IFNγ producing CD4 and CD8 increased at D+9^ | Macrophage and DC MHCII expression increased at D+9^ | NR | |
3 | CTLA-4 | CLP (C.a. D+3)## | IP and IV | NR | NR | NR | NR | |
Shindo, 2015 | 1 | PD-1 | CLP (C.a. D+3) ## | IP and IV | NR | Splenic NK, CD4, and CD8 intracellular IFNγ increased, cultured splenocyte IFNγ supernatant not different on D+9 | CD28 expression on LN CD4 increased on D+9^; CD28 on splenic CD4 and CD8 not differentns; splenic and LN macrophage and DC MHCII not different on D+9 | NR |
Cheng, 2016 | 1 | BTLA | CLP | IP | MIP-2 increased on D+1^ but TNFα, IL-1β, IL-6, IL-10, IL-12, KC, MCP-1 not differentns | Peritoneal lavage TNFα, IL-10, IL-12, KC, MIP-2, MCP-1 and peritoneal macrophage LPS-stim TNFα and MIP-2 increased on D+1^; IL-1β, IL-6 not different in peritoneal lavage on D+1 | Total peritoneal leukocyte and F4/80, CD11c+ and Gr1+ cells increased on D+1^ | Peritoneal total cell and macrophage apoptosis not different on D+1ns |
Shindo, 2017 | 1 | PD-1, PD-L1 | CLP (C.a. D+3)## | IP and IV | NR | NR | NR | NR |
Deng, 2018# | 1 | PD-L1 | CLP | IP | NR | NR | NR | Splenic CD4 and CD8 apoptosis decreased on D+2 and D+3^ |
2 | PD-L1 | CLP | IP | NR | NR | NR | Splenic CD4 and CD8 apoptosis decreased on D+2 and D+3^ | |
Patil, 2018 | 1 | PD-L1 | P. aer | ID | IL-6, IL-10, MIP-2, KC, IL-17 decreased on D+2^ | Spleen and LN CD8 IFNγ production increased, LN CD4 IFNγ production decreased on D+2^ but spleen CD4 IFNγ production not differentns | Spleen and LN CD4 and CD8 cell counts increased on D+2^. LN B cell numbers increased at D+2^, not different in spleen. CD28 expression on LN CD4+ and CD8+ increased at D+2^ | NR |
2 | PD-L1 | S. aur | IV | NR | NR | NR | NR |