Fig. 4.

Immunity therapies to fight sepsis. Immunomodulatory therapy includes medication to improve immunity and immune stimulation combined with anti-inflammatory approaches can significantly improve the outcome of severe sepsis. IFN-γ, GM-CSF and IL-7 are immunostimulatory cytokines that have been proven to activate early-responding immune cells in sepsis. IFN-γ and GM-CSF can activate innate immune cells to enhance phagocytosis in addition to pro-inflammatory cytokine release and the expression of mHLA-DR on APCs. IL-7 can increase the number of lymphocytes by promoting proliferation and inhibiting apoptosis. Immunoglobulin is a natural protein that neutralizes endotoxins in the body and promotes the phagocytic ability of monocytes and macrophages. Immunoglobulin therapy may be beneficial in improving the prognosis of septic patients with multidrug-resistant bacterial infections. Thymosin alpha1 can activate innate immune cells such as DCs and NK cells, and macrophages stimulate T-cell proliferation and enhance the antibacterial effect of Th1 cells. MSCs can promote the maturation of M2 macrophages and regulatory T cells, thereby promoting bacterial clearance and limiting excessive inflammation, to alleviate organ damage and ultimately reduce sepsis mortality. Coinhibitory molecule antibodies and antagonists targeting TIM-3, PD-1, BTLA, etc., can restore the function of innate and acquired immunocytes, reversing the immune exhaustion state. GM-CSF granulocyte–macrophage colony-stimulating factor, MSC mesenchymal stem cell, BTLA B and T lymphocyte attenuator, Mo/Mφ monocyte/macrophage, DC dendritic cell, NK natural killer cell, HLA-DR human leukocyte antigen-DR, LPS lipopolysaccharide, PD-1 programmed cell death 1, IFN-γ interferon-γ, IL interleukin