Abstract Sickness behavior associated with inflammation impairs quality of life and increases morbidity and mortality. However, the neural mechanism that mediates inflammation-associated changes are poorly understood. Here, we identify the bed nucleus of the stria terminalis (BNST) as a critical node in mediating responses to cytokines. Administration of recombinant interleukin-1β (rIL-1β) significantly increases serum IL-6 (control vs. rIL-1β; 22.6±4.7 vs 1,487±341.4 pg/ml; p=0.0079). A significant decrease in core body temperature (pre vs. post; 38.1±0.2 vs. 36.1±0.4oC; p<0.0001) and activity level (pre vs. post; 0.2±0.03 vs. 0.03±0.01 A.U.; p=0.0002) is also observed with rIL-1β administration. We visualized rIL-1β-responsive neurons using activity-dependent cell labeling, and identified distinct neuronal populations in the BNST that are active in response to IL-1β. Selective activation of IL-1β-responsive neurons using a chemogenetic approach is sufficient to induce significant increase in serum IL-6 levels (control vs. IL-1β; 26.2±74.1 vs. 272.5±8.3 pg/ml; p=0.01). Reactivation of IL-1β-responsive neurons also induces significant decrease in core body temperature (pre vs. post; 37.6±0.3 vs. 36.1±0.6oC; p=0.02) and activity levels (pre vs. post; 0.1±0.01 vs. 0.06±0.01 A.U.; p=0.02). Our data defines a neural population in the BNST that is sufficient for mediating IL-1β-associated responses, revealing its role in the coordination of inflammatory responses.
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