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Glycerophosphoinositols in the septic shock

anti-inflammatoryglycerophosphoinositolslipopolysaccharidesepsistissue-factor

Introduction

The present invention relates to glycerophosphoinositols (GPIs) and derivatives thereof for use in the treatment of pathologies related to a Lipopolysaccharide (LPS)-activated tissue-factor (TF) activity, as pathologies induced by high bacteremia, i.e. septic shock.

Technical features

Sepsis syndrome (sepsis) is an adverse systemic response to infection that includes low blood pressure, rapid heartbeat and respiration, fever, and organ dysfunction associated with compromised blood circulation. Sepsis can occur through infection by bacteria, fungi and viruses, or secreted toxins. However, the sepsis syndrome occurs commonly in response to lipopolysaccharides (LPS), major constituents of Gram-negative bacterial cell wall and essential for the membrane structure and integrity. Glycerophosphoinositols (GPIs) are natural compounds which regulates different cellular activities. The authors suggest and demonstrate the use of GPIs to reduce pro-inflammatory and pro-thrombotic responses in human monocytes stimulated with LPS. GPI can counteract LPS immunophatological features by regulating in a negative manner the expression of pro-inflammatory and pro-thrombotic genes which cause the septic syndrome.

Possible Applications

  • Treatment, prevention or reducing the severity of a symptom of sepsis, severe sepsis, septic shock induced by LPS of Gram-negative bacteria, and comprising symptoms as disorders of coagulation and/or disseminated intravascular coagulation.

Advantages

GPIs are:

  • small natural molecules, non-toxic, water-soluble, permeable (by permease) to the plasma membrane
  • easily obtainable by synthesis or extraction.
  • well-suitable to the demands of modern pharmacology.