The Brigham and Women's Hospital, Inc.

Nan Chiang

Charles Nicholas Serhan

Jesmond P Dalli

Paul Norris

Disclosed herein is a method of providing a metabololipidomic profile and SPM signature on the progress of the innate host defense response following blood clotting. The method can include the step of taking one or more measurements in a patient's blood sample, wherein the sample is obtained during the time-course of clotting or coagulation or following clotting or coagulation, of pro-thrombotic and pro-inflammatory mediators (eicosanoids) and specialized pro-resolving mediators SPMs. From these measurements, a personalized metabololipidomic profile can be obtained. By comparing the measurement to that taken from normal or reference blood, a comparison profile can be developed. The profile comparison profile can then be used to make a medical or therapeutic decision.

Personalized metabolomic profiling of specialized pro-resolving mediators

New host-protective molecules containing conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5) were produced in neutrophil-endothelial co-cultures, and they are present in human and mouse tissues after sterile inflammation or infection. These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival duringinfections. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. Atorvastatin and RvT were additive ininfections in mice where they accelerated resolution of inflammation and increased survival &#x3e;60%. Results documented novel host protective molecules in bacterial infections, namely RvT, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components to regulate key innate protective responses in the resolution of infectious-inflammation.

Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections

A family of bioactive compounds identified in self-resolving inflammatory exudates is disclosed. The compounds give UV chromophores characteristics of a conjugated triene double bond system coupled to an auxochrome allylic to the triene. Further elucidation of the compounds reveals that they have an oxylipin backbone conjugated to a peptide or amino acid moiety via an auxochrome. In some embodiments the auxochrome is sulfur. However, the auxochrome may be NH, CH2 or O. The compounds have potent bioactivity, in vitro, and, in vivo, including promoting resolution of infection, stimulating macrophage phagocytosis of bacteria; protecting tissues from neutrophil mediated damage, promoting tissue repair and regeneration and preventing or limiting second organ reflow/reperfusion damage.

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Somerville, MA, United States of America

Nan Chiang