Sepsis Immunopathology: Perspectives of Monitoring and Modulation of the Immune Disturbances

Abstract

Septic syndromes are the main cause of death in the intensive care units and although the mortality rates is slowly decreasing, the occurrence of the disease has been increasing. The pathogenesis of sepsis includes countless disturbances of the host immune system starting with a harmful, infection-triggered exaggerated inflammatory cascade, followed by the development of an immunoparalysis state. The latter contributes to the failure in pathogen eradication and leads to secondary infections, which are often the cause of fatal complications. In this review, we consider different novel therapeutic strategies for restoration of immune function. The use of glucocorticoids, intravenous immunoglobulins, heparin, recombinant human activated protein C, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-γ, statins, macrolides and high-volume hemofiltration are discussed. Even though some clinical trials of these regimens are promising, the key to their successful application seems to be the precise monitoring of the status of immune system followed by implementation of the adequate therapy. Thus, in this paper we present disturbances in the immune system in the course of human sepsis, with special attention to the parameters that could be monitored and serve as markers for immunomodulatory therapies. We conclude by briefly presenting the current sepsis treatment strategy.

Human macrophage and dendritic cell-specific silencing of high-mobility group protein B1 ameliorates sepsis in a humanized mouse model

“…The pathogenesis of sepsis includes countless disturbances of the host immune system starting with a harmful, infection-triggered exaggerated inflammatory cascade that results in tissue injury and rapidly leads to massive apoptosis of immune cells (2,3). This is followed by a secondary immune paralysis phase accompanied by uncontrolled growth of bacteria and tissue damage.…”

Anti-Inflammatory Cytokines in Sepsis: Immunological Studies and In Silico Investigation

“…The implementation of the cytokines in AutoSimmune (immune system simulator) is performed as values scattered in arrays of data parallel to the agent interaction environment [18].…”

“…Each agent has access to the concentration of each substance dispersed in that instant, to its position, through these matrixes, as well as, to secrete more substances [18].…”

Pro-Inflammatory Cytokines in Sepsis: Biological Studies and Prospects From In Silico Research

“…The IL-17 family of cytokines has emerged as important mediator of immune regulation, since it cooperates with the pro-inflammatory response by triggering the production of other cytokines such as IL-1β, IL-6 and TNF-α, in addition to signaling between lymphocytes and phagocytes [18,27,28]. Additionally in patients with severe sepsis, high levels of IL-1α, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1) and granulocyte colony-stimulating factor (G-CSF) are associated with lethality [29].…”

“…There are two abstract groups of cytokines in the system, based on their functionality. The first is represented by pro-inflammatory cytokines, which amplify inflammatory responses, and the second is made up of anti-inflammatory cytokines which suppress the inflammatory response [18]. Studies using AutoSimmune are currently under development, with this configuration, with some preliminary results published [25,42,43].…”