PGC-1 alpha is a Valuable Tool to Differentiate Inflammation From Infection in Acute Pancreatitis

Abstract

Background: Differentiate sepsis from the systemic inflammation caused by AP remains a clinical challenge. We hypothesized that transcription coactivator PGC-1>, a regulator of mitochondrial biogenesis and function, would be distinctly expressed during inflammation or infection, being useful to differentiate these two conditions. Methods: Acute pancreatitis(AP) was induced by retrograde injection o,5 ml of 5% sodium taurocholate into the main pancreatic duct.. PGC-1> mRNA.was evaluated by using a quantitayive Real-time PCR Macrophages were obtained by washing the peritoneum with PBS and placed in culture for 2h. and exposed to lipopolysaccharide, zymosan or vehicle. In another set of experiments, macrophages were transfected with antisense against PGC-1> Cecal ligation puncture (CLP) was used to establish a model of infected peritonitis. Results: In AP animals a marked increase in PGC-1> mRNA levels in circulating leukocytes was observed 48h after the surgical procedure, a time when bacteremia is present. Antibiotic treatment abolished PGC-1> up-regulation. Moreover, PGC-1> expression was higher in peritoneal macrophages from animals submitted to a bacterial insult (CLP) than in animals with acute pancreatitis .In macrophages, we could observe that PGC-1> expression is more prominent in the presence of a phagocytic stimulus (zymosan) compared to an aseptic inflammation induce by lipopolysaccharide. Moreover, abolishing PGC-1> expression with antisense impaired zymosan phagocytosis. Conclusion: Together these findings suggest that PGC-1> is differentially expressed during aseptic inflammation and infection and that it is necessary for adequate phagocytosis. These results could be useful in developing new tests for differentiating infection from inflammation in patients with acute pancreatitis.