Insights and limits of translational research in critical care medicine

Annals of Intensive Care

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.