Beneficial effects of finasteride on hepatic and pulmonary immune response after trauma hemorrhage in mice

Abstract

The literature reveals evidence for a gender specific outcome after major trauma and hemorrhage. Increased levels of male sex hormones such as testosterone and even more dihydrotestosterone (DHT) mediate negative effects on the posttraumatic immune response. Pretreatment with finasteride several days before trauma hemorrhage (TH) led to improved outcomes in mice. We hypothesized that finasteride mediates its protective effects also when administered after TH within the resuscitation process. MethodsMale C57BL/6N-mice underwent TH (blood pressure: 35mmHg, 90min) followed by finasteride application and fluid resuscitation. Plasma cytokines (MIP-1β, TNF-α, MCP-1, MCP-3, IL-6), productive capacity of alveolar macrophages (AM) and hepatic Kupffer cells (KC) and systemic DHT levels were determined 4h and 24h thereafter. Pulmonary and hepatic infiltration of PMN was determined by immunohistochemical staining. ResultsFinasteride treatment resulted in reduced levels of systemic cytokines. This was accompanied by a reduced posttraumatic cytokine secretion of AM as well as Kupffer cells, thereby reducing hepatic distant organ damage as measured by reduced PMN infiltration. Systemic DHT levels were decreased following finasteride treatment. ConclusionFinasteride exerts salutary effects on the pulmonary and hepatic immune response using a therapeutic approach following TH in mice. Therefore, finasteride might represent a potential agent following multiple trauma and hemorrhage.