490. Brain-derived neurotrophic factor (BDNF) is a prognostic biomarker and therapeutic target through AMP-activated protein kinase (AMPK) signal pathway for sepsis

Abstract

Abstract Background Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine that not only acts on the central nervous system, but is also implicated in metabolic regulation, development of lung diseases, and support of hematopoiesis. Recently, a study report that the plasma levels of BDNF were independently associated with mortality in critically ill patients. We aimed to evaluate the role of BDNF in sepsis patients and animal sepsis model. Methods Prospectively enrolled adult sepsis patients (n=168) who visited the emergency room (ER) of Korea University Ansan Hospital from January 2017 to December 2018., and healthy volunteers (n=48) were included in the present study. Serum BDNF level was determined and analyzed in septic patients and healthy volunteers. The effects of BDNF on pro-inflammatory cytokines, AMP-activated protein kinase (AMPK) and NF-κB signaling in septic condition of RAW264.7 cells and mouse peritoneal macrophage, and mouse sepsis model by cecal ligation and puncture (CLP). Results Serum BDNF levels (mean) were significantly decreased in sepsis patients compared to healthy controls (11.78ng/ml vs 18.91ng/ml, p< 0.001) and significantly decreased in non-survivors compared to survivors at discharge (3.16ng/ml vs 13.86ng/ml, p< 0.05). BDNF treatment suppressed LPS-induced pro-inflammatory cytokine (TNF-α, iL-6, and iL-1β) in RAW264.7 cells. Although LPS stimulation diminished AMPK phosphorylation, BDNF was able to decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on down stream signaling events, particularly LPS-induced IκBα degradation in RAW cells and peritoneal macrophage. In CLP model, intra-muscular injection of BDNF after CLP significantly decreased serum levels of TNF-α which was increased compared to sham, and significantly improved survival of mouse (p< 0.01). Conclusion Sepsis results in a decreased production of BDNF, which might be a potential prognostic biomarker and therapeutic target through AMPK signal pathway for sepsis. Disclosures All Authors: No reported disclosures.