TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia

Brain, Behavior, and Immunity
Kevin G BurfeindDaniel L Marks

Abstract

Hypothalamic inflammation is a key component of acute sickness behavior and cachexia, yet mechanisms of inflammatory signaling in the central nervous system remain unclear. Previous work from our lab and others showed that while MyD88 is an important inflammatory signaling pathway for sickness behavior, MyD88 knockout (MyD88KO) mice still experience sickness behavior after inflammatory stimuli challenge. We found that after systemic lipopolysaccharide (LPS) challenge, MyD88KO mice showed elevated expression of several cytokine and chemokine genes in the hypothalamus. We therefore assessed the role of an additional inflammatory signaling pathway, TRIF, in acute inflammation (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. Lastly, we found that TRIF was required fo...Continue Reading

Citations

Jun 17, 2020·The Journal of Clinical Investigation·Xinxia ZhuDaniel L Marks
Oct 3, 2020·Journal of Cachexia, Sarcopenia and Muscle·Paul T WinnardZaver M Bhujwalla
Jan 29, 2019·Frontiers in Psychiatry·Carsten CulmseeJudith Alferink
Feb 20, 2021·Cancer Treatment and Research Communications·Timotius Ivan Hariyanto, Andree Kurniawan
Mar 13, 2021·Biochemical Pharmacology·Raquel D S Freitas, Maria M Campos
Apr 8, 2021·Nature Communications·Brennan OlsonDaniel L Marks
Jun 26, 2021·Pharmacology & Therapeutics·Cong LinXiaohui Wang
Jul 11, 2021·Brain, Behavior, and Immunity·Brennan OlsonDaniel L Marks
Aug 28, 2021·Cancers·Brennan OlsonDaniel L Marks
Aug 22, 2021·Brain, Behavior, and Immunity·Elisabeth G VichayaRobert Dantzer

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