PT  - JOURNAL ARTICLE
AU  - Kevin G. Burfeind
AU  - Xinxia Zhu
AU  - Peter R. Levasseur
AU  - Katherine A. Michaelis
AU  - Mason A. Norgard
AU  - Daniel L. Marks
TI  - “TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia”
AID  - 10.1101/232280
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 232280
4099  - http://biorxiv.org/content/early/2017/12/11/232280.short
4100  - http://biorxiv.org/content/early/2017/12/11/232280.full
AB  - Hypothalamic inflammation is a key component of acute sickness behavior and cachexia, yet mechanisms of inflammatory signaling in the central nervous system remain unclear. We assessed the role of TRIF signaling in acute inflammation (lipopolysaccharide (LPS) challenge) and in a chronic inflammatory state (cancer cachexia). TRIFKO mice resisted anorexia and weight loss after peripheral (intraperitoneal, IP) or central (intracerebroventricular, ICV) LPS challenge and in a model of pancreatic cancer cachexia. Compared to WT mice, TRIFKO mice showed attenuated upregulation of Il6, Ccl2, Ccl5, Cxcl1, Cxcl2, and Cxcl10 in the hypothalamus after IP LPS treatment, as well as attenuated microglial activation and neutrophil infiltration into the brain after ICV LPS treatment. Our results show that TRIF is an important inflammatory signaling mediator of sickness behavior and cachexia and presents a novel therapeutic target for these conditions.