Molecular biology of inflammation and sepsis: A primer*

Abstract

Many of these basic discoveries have direct implications for the clinical management of sepsis. The translation of these "bench-to-bedside" findings into new therapeutic strategies is already underway. This brief review provides the clinician with a primer into the basic mechanisms responsible for the molecular biology of sepsis, severe sepsis, and septic shock.

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

“…Central to apoptosis are caspases, which are cysteine proteases that degrade cellular proteins and nuclear factor‐kappa B (NF‐κB), a transcription factor that activates the transcription of both proapoptotic and prosurvival genes. Whereas hyper‐inflammatory responses of sepsis require NF‐κB for the production of proinflammatory cytokines and the activation by caspase cleavage, both NF‐κB and caspases concurrently induce the apoptosis of immune cells 3. Consistent with this, a concurrent apoptotic response has been shown to be present in sepsis in association with the proinflammatory response 13…”

“…This initial immune recognition response is mediated by pathogen‐associated molecular patterns and damage‐associated molecular patterns originating from bacterial or fungal organisms that blind pattern recognition receptors expressed on innate immune cells 3. The activation of pattern recognition receptors results in the production of numerous proinflammatory cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐8, and interferon (IFN)‐γ and anti‐inflammatory cytokines that induce excessive hyper‐inflammatory responses and counter‐responses.…”

Postoperative Accumulation of Cyr61/CCN1 in Surgical Wound Fluid Precedes Cytokine Activation and is Disparate from Systemic Alterations

“…If the injury/ infection is excessive, however, the response may disseminate into the systemic inflammatory response syndrome with the potential for causing distant organ dysfunction [1,2]. Hence, the mechanisms underlying this potentially lethal transition are, to a large extent, the consequence of the collateral damage imposed by an exaggerated host response [3,4]. Major surgical procedures and severe infections may provoke this transition from normal and beneficial inflammation to catastrophic scenarios [5], but the exact mechanisms underlying this transition remain poorly understood and warrant further investigation, particularly with regard to the molecular biology of acute inflammation.…”

Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis

“…The pathophysiology of sepsis-associated DIC is very complex and has been exhaustively examinated. The major occurrence is the systemic inflammatory reaction to the infectious agent (Tsujimoto et al, 2008;Cinel & Opal, 2009). This syndrome may be promoted by the microorganism expressing unique cellular components, known as pathogen-associated molecular patterns (PAMPs).…”