cachexia

Introduction

blocking IL-6 from binding to neurons in a part of the brain called the area postrema (AP) prevents cachexia in mice, this worked by either:¹⁾
- neutralized IL-6 with custom antibodies
- using CRISPR to reduce the levels of IL-6 receptors in AP neurons
see also: interleukin-6 (IL-6)

growth differentiation factor 15 (GDF15) is a stress hormone which can trigger nausea by binding to GFRAL receptors in the brainstem and is a potent anorectic factor
sensitivity to GDF15 is the cause of hyperemesis gravidarum and serum levels can also be 10-100x higher than normal in patients with advanced cancers

cancer-induced systemic inflammation disrupts vagal tone via increased CCL2/CCR chemokine acting in the CNS
this dysregulation leads to reduced acetylcholine release from vagal synapses and resulting depletion of hepatic HNF4α, a crucial transcription factor governing liver protein metabolism
the resulting hepatic dysfunction amplifies systemic inflammation, driving the cachectic symptoms that afflict many cancer patients
restoring vagal function by targeting the right cervical vagus nerve reestablished normal liver metabolism, reduced systemic inflammation, and alleviated cachexia's clinical manifestations ²⁾

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