Targeting sepsis through inflammation and oxidative metabolism

Table 1 Summary of presented targets

Target	Agonism/antagonism	Proposed mechanism
IFN-	Agonism	Reversal of sepsis-based immunosuppression by promotion of Warburg effect, inflammatory cytokine production and HLA-DR expression
GM-CSF	Agonism	Promotions of neutrophil and monocyte phagocytic function in sepsis
IL-7	Agonism	Promotions of T-cell activation and suppression of T-cell apoptosis in sepsis
IL-15	Agonism	Promotion of T-cell function and survival in sepsis
IL-6	Antagonism	Unclear; associated with anti-inflammatory cytokine production
TGF-β	Agonism	Promotion of T-cell and macrophage activation, proliferation and differentiation
Immunoglobulin	N/A	Neutralize toxins, enhance opsonization, and interact with complement components to minimize nonspecific activation
Thymosin α1	Agonism	Enhance T-cell function
Mesenchymal stem cells	N/A	Potential to differentiate to different immune cell lineages, modulating to specific host need
PD1/PD-L1	Antagonism	Promoted T-cell survival and function
Corticosteroids	N/A	Suppression of the immune response, pro-inflammatory cytokine production and modulation of vascular permeability
Norepinephrine	N/A	Unclear; mediates sympathetic nervous system response to infection by immune cell modulation; improve vascular permeability
Beta blockers	N/A	Unclear
Glycocalyx	N/A	Maintain vascular permeability and function to promote leukocyte adhesion and function
Vitamin C	N/A	Reduction of inflammation by modulating pro-inflammatory cytokine release
NAC	N/A	Reduction of inflammation by modulating pro-inflammatory cytokine release

PD-1: Programed cell death-1; PD-L1: Programmed cell death ligand-1; NAC: N-acetyl cysteine; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFN: Interferon; IL: Interleukin; TGF: Transforming growth factor.