Table 2.
Therapeutic targets and potential treatments of sepsis-induced immunosuppression
| Biomarker | Potential therapeutics | Clinical data | Comments |
|---|---|---|---|
| Monocyte deactivation | GM-CSF | Yes | Restoration of HLA-DR expression [39,83] |
| Clearance of uncontrolled infections [83] | |||
| Reduced duration of mechanical ventilation [39] | |||
| IFN-γ | Yes | Restoration of HLA-DR expression [38] | |
| Apoptosis of immune cells | Anti-apoptotic cytokines | No | |
| Caspase inhibitors | No | ||
| Death-receptor antagonists | No | ||
| Increased Tregs | Anti-Tregs antibodies | No | |
| Depletion/deactivation of dendritic cell | Flt3-L | No | |
| TLR-agonists | No | ||
| T cell exhaustion | IL-7 | Yes | Ex vivo restoration of lymphocyte functions [40] |
| Thymosin-α | Yes | Improved survival in sepsis due to carbapenem-resistant bacteria (in association with ulinastatin) [84] | |
| IL-15 | No | ||
| Upregulated expression of co-inhibitory receptors | Monoclonal antibodies: | ||
| Anti-PD1/PDL1 | No | ||
| Anti-CTLA-4 | No | ||
| Anti-BTLA | No |
GM-CSF, granulocyte-monocyte colony-stimulating factor; IFN-γ, interferon-γ; HLA-DR, human leukocyte antigen-DR; Tregs, T regulatory lymphocytes; Flt3-L, ligand of the fms-like tyrosine kinase 3; TLR, Toll-like receptor; IL, interleukin; PD1, programmed death 1; PDL1, programmed death ligand 1; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; BTLA, B and T lymphocyte attenuator.