Sepsis is a severe morbid condition, characterized by a set of immunological, metabolic, haemodynamic and respiratory abnormalities, secondary to an infectious process, associated with a systemic inflammatory response state (SIRS) in the host organism.
So it is a systemic response to an attack by an external agent, usually a microorganism, characterized by inflammation, by alteration of the coagulation system and by immunoparalysis.
Sepsis is one of the leading causes of death in Intensive Care Units.

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The physiopathogenesis of sepsis is complex and, to date, not fully understood.
Several different pathogens are responsible for the development of sepsis.
The microorganisms most frequently involved are gram-positive bacteria, followed by gram-negative bacteria and fungi.

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When the body is invaded by these microorganisms, pro- and anti-inflammatory mediators are released. When such release is excessive, uncontrolled and spreads beyond the site of infection, sepsis develops which evolves into its more severe forms, such as septic shock and multi organ dysfunction syndrome – MODS, in many cases leading to death. Mortality rates in sepsis are related to its severity.

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The main inflammatory mediators involved in the development and evolution of septicaemia are the cytokines.
These protein molecules alter the behaviour of other cells, leading to diverse cellular activities such as growth, differentiation and death.

Role of cytokines

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Excessive and uncontrolled production of cytokines, including IL-6, IL-1ß, IL-8, IL-10, TNF-α., known as a cytokine storm, propagates inflammation from the site of infection throughout the body, affecting the severity and outcome of the evolution of sepsis itself.

The cytokine storm is characterized by cytokine levels that are toxic to the body, responsible for the pathophysiological, inflammatory and haemodynamic changes typical of sepsis, such as cell damage and organ failure. Once started, the cytokine storm is difficult to stop, even when its primary cause is removed, as it is a self-perpetuating process.

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This means that, in order to modulate the body’s inflammatory response, by controlling the clinical evolution of septicaemia, the spread of the cytokine storm must be stemmed, restoring the balance between pro- and anti-inflammatory mediators.

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