Therapeutic potential of plasma gelsolin administration in a rat model of sepsis.

BACKGROUND Gelsolin is an actin-binding protein found in the cytoplasm and in extracellular fluids including blood plasma. Plasma gelsolin concentration decreases after a wide range of injuries. We hypothesized that the repletion of gelsolin would limit inflammation and tissue injury in a rat model of sepsis using cecal ligation and double puncture (2CLP). METHODS Human plasma gelsolin (pGSN, 10mg in 1ml saline) was administered once immediately following surgery, and control 2CLP (2CLP Alb) and sham animals were injected with 1ml saline containing equimolar albumin. Treatments were administered intraperitoneally (IP), intravenously (IV), or subcutaneously (SC). RESULTS Gelsolin levels in the 2CLP Alb group were lower than in sham animals. Administration of pGSN increased levels when administered IV and SC, but not IP. Morbidity scores were significantly less severe in the 2CLP pGSN group than in the 2CLP Alb group when pGSN was administered IV and SC, but not IP. Furthermore, enzymatic activity indicative of tissue damage (lactate dehydrogenase and alanine transaminase) was significantly lower in 2CLP pGSN group when treated SC compared to 2CLP Alb group. CONCLUSION These data provide further evidence that exogenous gelsolin can reduce morbidity from sepsis.