Sepsis: From Historical Aspects to Novel Vistas. Pathogenic and Therapeutic Considerations

Abstract

Background: Sepsis is a clinical condition due to an infectious event which leads to an early hyper-inflammatory phase followed by a status of tolerance or immune paralysis. Hyper-inflammation derives from a massive activation of immune (neutrophils, monocytes/macrophages, dendritic cells and lymphocytes) and non-immune cells (platelets and endothelial cells) in response to Gram-negative and Gram-positive bacteria and fungi.

Discussion: A storm of pro-inflammatory cytokines and reactive oxygen species accounts for the systemic inflammatory response syndrome. In this phase, bacterial clearance may be associated with a severe organ failure development. Tolerance or compensatory anti-inflammatory response syndrome (CARS) depends on the production of anti-inflammatory mediators, such as interleukin-10, secreted by T regulatory cells. However, once triggered, CARS, if prolonged, may also be detrimental to the host, thus reducing bacterial clearance.

Conclusion: In this review, the description of pathogenic mechanisms of sepsis is propaedeutic to the illustration of novel therapeutic attempts for the prevention or attenuation of experimental sepsis as well as of clinical trials. In this direction, inhibitors of NF-κB pathway, cell therapy and use of dietary products in sepsis will be described in detail.

Keywords: Bacteria; cytokines; fungi; inflammation; sepsis; therapy; tolerance..