Mediators of sepsis-induced immunosuppression

Sepsis-induced immunosuppression, often called immunoparalysis, is a complex systemic state of impaired immune function that occurs after the initial hyper-inflammatory phase of sepsis, leading to increased susceptibility to secondary infections and higher mortality (Hotchkiss et al., 2013, Lancet Infectious Diseases). This condition is driven by various mediators, including the upregulation of inhibitory immune checkpoint proteins like Programmed cell death protein 1 (PD-1), Programmed death-ligand 1 (PD-L1), and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), as well as the release of anti-inflammatory cytokines such as Interleukin-10 (IL-10) and Transforming growth factor-beta (TGF-β) (Rubio et al., 2019, Journal of Clinical Investigation). These factors contribute to the exhaustion and apoptosis of T-cells and B-cells and the downregulation of Human Leukocyte Antigen-DR (mHLA-DR) on monocytes, which severely impairs antigen presentation (Delano and Ward, 2016, Nature Reviews Immunology). Therapeutic strategies currently target these mediators using monoclonal antibodies against PD-1/PD-L1 or by administering recombinant immunostimulatory cytokines like Interleukin-7 (IL-7) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) to restore immune competence (Venet and Monneret, 2018, Expert Review of Clinical Immunology). While promising, these interventions face the challenge of precisely timing delivery to avoid re-igniting hyper-inflammation or inducing autoimmune-like tissue damage in critically ill patients (Adib-Conquy et al., 2020, Frontiers in Immunology).

Other names

Sepsis-induced immunoparalysis mediatorsImmune dysfunction mediators in sepsisImmunosuppressive factors in sepsis

Blockade of inhibitory checkpoint receptors (e.g., PD-1/PD-L1) or administration of immunostimulatory cytokines (e.g., IL-7, GM-CSF) to reverse immune exhaustion and restore the host's capacity to clear infections.