Remedy for Systemic Inflammatory Response Syndrome (SIRS)
Injury results in release of cytoplasmic ATP, which is sensed by monocytes/macrophages via ATP receptor P2X7. This swiftly induces inflammasome activation, caspase-1-dependent cleavage and release of interleukin-1ß (IL-1ß), IL-18 and HMGB1. Excessive systemic IL-1ß release is the first stage of a reaction chain causing SIRS and high patient mortality.
IL-1ß is involved in host defense against infections. Pathogen-induced inflammasome activation, however, typically involve ATP-independent pathways. Hence, a-1-antitrypsin, SLPI, CRP, and DPPC inhibit injury induced inflammation but do not inhibit clearance of pathogens.
Scope of application: SIRS, Major surgery, Trauma, Extracorporeal circulation (e.g. cardiopulmonary bypass, ECMO), Chronic inflammation, Lung injury
SIRS-related multi organ dysfunction (MODS) and acute lung injury (ALI) are among the leading causes of death worldwide. The proposed remedies have the potential to become affordable life-saving medicaments for numerous indications.
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