Table 2.

Current clinical evidence for immunostimulation in patients with sepsis.

Therapy	Goal of therapy	Human Evidence	References
G-CSF/ GM-CSF	Accelerate innate immune cell production Restore mHLA-DR expression and cytokine production	Enhanced resolution of infection1 Decreased length of ICU stay1 Minimal adverse events1 May be delivered directly to lung2 Pending results from phase III clinical trial3	Bo et al. (157) Scott et al. (158) NCT02361528
IFNγ	Increase phagocytic capacity Restore mHLA-DR expression and cytokine production	Enhanced resolution of bacterial and fungal infection (case series)1, 2 Pending results from phase IIIb trial3	Nalos et al. (159) Delsing et al. (160) NCT01649921
IL-7	Accelerate lymphocyte production Decrease lymphocyte apoptosis	Well tolerated in phase IIb trial1 Increased CD4+ and CD8+ lymphocytes1 Increased T cell activation and trafficking1	Francois et al. (161)
Anti-PD-1/ PD-L1	Reverse innate and adaptive immune exhaustion Restore mHLA-DR expression and cytokine production	Well tolerated in patients with sepsis and septic shock1 Trend toward sustained restoration of mHLA-DR1 Pending results from phase Ib trial2	Hotchkiss et al. (162) NCT02960854
Tα1	Restore mHLA-DR expression	No adverse events reported in single RCT1 Trend toward improved 28-day mortality1 Ongoing phase III clinical trial2	Wu et al. (163) NCT02883595
MSC	Reduce inflammatory response Decrease lymphocyte apoptosis Increase phagocytic capacity	No adverse events reported in a phase I clinical trial1 Ongoing phase II clinical trial2	McIntyre et al. (164) NCT02883803

Tα1, Thymosin alpha 1; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte-macrophage stimulating factor; IFNγ, interferon gamma; MSC, mesynchymal stem cell; NCT, clinicaltrials.gov identifier.