Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome

Philip Toner, Danny Francis McAuley, Murali Shyamsundar, Philip Toner, Danny Francis McAuley, Murali Shyamsundar

Abstract

Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS.

Trial registration: ClinicalTrials.gov NCT01659307 NCT02326350.

Figures

Fig. 1
Fig. 1
Mechanisms in which aspirin can manipulate the process in sepsis and acute respiratory distress syndrome: Inhibit the enzyme COX, preventing the formation of pro-inflammatory thromboxane and prostaglandins. Inhibit the release of NFκB from its inhibitor IkB, preventing the formation of pro-inflammatory cytokines and chemokines. Production of aspirin triggered lipoxin, which induces the release of NO, inhibits production of IL-8 and MPO, restores neutrophil apoptosis and promotes resolution. Increase production of NO, resulting in reduced migration and infiltration of neutrophils and reduced permeability of endothelium. 15-epi-ATL, aspirin-triggered 15-epi-lipoxin A4, AA arachidonic acid, COX cyclooxygenase, eNO endothelial nitric oxide, IKK IkB kinase, IL-8 interleukin 8, MPO myeloperoxidase, NFκB nuclear factor kappa B, NO nitric oxide, PGE2 prostaglandin E2, TXA2 thromboxane

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