# Central neurons encode interleukin-1β signals and mediate stress-induced inflammation

## TL;DR

The brain uses a specific neural circuit to detect and respond to the inflammation-related molecule IL-1β, linking stress to physiological changes like increased heart rate and inflammation.

## Contribution

This study identifies a specific neural circuit in the brain that encodes IL-1β signals and mediates systemic stress responses.

## Key findings

- IL-1β signals are encoded by corticotropin-releasing hormone-expressing neurons in the BNST.
- Activating these neurons reproduces physiological effects of IL-1β exposure, including elevated IL-6 and corticosterone.
- Restraint stress activates the same neurons through a defined brain pathway to produce systemic responses.

## Abstract

Although sensory nerves respond differentially to individual inflammatory cytokines, it is unknown whether these relay to distinct central circuits governing physiological responses. This work identifies such a circuit in which IL-1β–responsive neurons control multiple components of the stress response.

The brain encodes and stores information about peripheral inflammation and can directly recapitulate prior inflammatory responses. However, whether individual cytokines activate specific neural circuits to produce distinct physiological responses remains unknown. To address this fundamental question, we mapped brain-wide responses to IL-1β and found prominent engagement of the bed nucleus of the stria terminalis (BNST). Using targeted recombination in active populations, snRNA sequencing, and circuit tracing, we discovered that corticotropin-releasing hormone-expressing BNST neurons encode IL-1β signals. Chemogenetic reactivation of these neurons precisely recapitulates the physiological signatures of IL-1β exposure with increased circulating IL-6 and corticosterone and tachycardia. These responses require a defined BNST→paraventricular nucleus→rostral ventrolateral medulla→β receptor adrenergic signaling pathway. Critically, restraint stress also activates these BNST IL-1β–encoding neurons to generate the same physiological responses. Our findings establish how a single inflammatory mediator uses a precise neural circuit to activate systemic responses and provide mechanistic insight into the neuroimmune interactions underlying stress-related psychiatric and inflammatory diseases.