Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Abstract

Sepsis affects the immune system by directly altering the lifespan, production, and function of the effector cells responsible for Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.

Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis

“…Sepsis is considered a dysregulated systemic inflammatory response syndrome caused by an infection, leading to an overwhelming and sustained proinflammatory state and, if unresolved, to multiorgan dysfunction (MOD) and death (2). Such a dysfunctional host inflammatory response is triggered by conserved structures present on microbial cell walls named pathogen-associated molecular patterns (PAMPs).…”

WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice

“…4 However, the failure of many clinical trials for adjunctive therapies for sepsis encourages reevaluation of the molecular drivers of sepsis-associated inflammation and pathology. 5,6 WNT ligands are secreted glycoproteins with well-characterized functions during embryogenesis and tissue homeostasis, where they orchestrate cell proliferation and polarization. 7 The 19 mammalian WNT ligands exhibit substantial conservation with regard to protein sequences and functions between humans and mice.…”

Insight into the Glucose Metabolism of Immune Cells in Sepsis

“…Therefore, regulating the Warburg effect may be a new direction for exploring the effective treatment of sepsis according to the metabolic response of the patients to infection. Interferon (IFN) -γ is the only member of the type II IFN family and has a key role in the immune defense against viruses, bacteria and protozoal infections (10). The laboratory study revealed that IFN-γ could restore the ability of endotoxin tolerance monocytes to stimulate the Warburg effect through the mTOR pathway (19).…”

“…However, the mortality at late stage of sepsis is still high (10). The pathophysiological mechanisms become much complicated due to immunosuppression and/or secondary infection at the late stage (several days to a few weeks after being diagnosed as sepsis) in septic patients.…”

“…In patients with sepsis, the early prognosis is significantly improved by antibiotic therapy as soon as possible, the maintenance of effective hemodynamic stability, and so on (10,11). However, most surviving patients show a number of characteristics of immunosuppression including apoptotic depletion of immune effector cells and increased expression of negative costimulatory molecules (12,13).…”