Classical descriptions of endotoxic shock and the discovery that inflammatory mediators such as TNF-alpha cause a shock-like condition led to the hypothesis that sepsis was driven by a hyper-inflammatory immune response. This paradigm resulted in more than 50 failed clinical trials and led to a reevaluation of the role of the immune system in sepsis. Contemporary data demonstrates that septic patients are immunocompromised, which manifests in an increased susceptibility to infection. Mechanisms of sepsis-induced immunosuppression include neutrophil and monocytes dysfunction, lymphocytes apoptosis, an expansion of immunosuppressive and anergic lymphocyte populations and mobilization of myeloid-derived suppressor cells out of the bone marrow. Next generation sepsis therapies will require better characterization of immune function in the patient, and potential immunophenotyping metrics include the measurement of circulating cytokine levels, ex-vivo cytokine production by leukocytes and monocyte human leukocyte antigen type DR (mHLA-DR) expression. An accurate understanding of the immune status of individual patients during sepsis will be critical to developing the next generation of immunomodulatory therapies.
|Title of host publication||Evidence-Based Practice of Critical Care|
|State||Published - Jan 1 2019|
- Immune dysfunction
- Myeloid-derived suppressor cells
- Secondary infection