Social isolation intensifies sickness severity and alters immune and neural activity responses 9223

Abstract Description During infection, the immune system and brain coordinate to eliminate pathogens and promote recovery. Despite the crucial role of neuroimmune communication in sickness pathology, the underlying mechanisms are unclear, partially due to individual variability in sickness severity. While many factors influence sickness, social isolation is known to negatively affect immune and brain function. Here, we investigated how prior social environment affects later sickness symptoms and underlying immune and neural activity. To induce sickness, male and female mice were chronically isolated or group-housed prior to a peripheral injection of lipopolysaccharide (LPS, 0.5 mg/kg). After the LPS challenge, isolated male mice exhibited exacerbated sickness symptoms, including greater hypothermia and prolonged anorexia, compared to their grouped counterparts. Activity pattern analysis found that co-housed sick males exhibited unique activity patterns in the insular cortex (IC), a region that integrates sensory, social, and immune signals. Increased IC activity in group-housed mice was correlated with decreased plasma concentration of pro-inflammatory cytokines that are known to induce sickness behaviors, including TNFα, IL-1β, and IL-6. In contrast, isolated males displayed a more severe and prolonged cytokine response, suggesting dysregulated immune activation. Together, these findings highlight the role of social context in shaping individual immune and neuronal responses to infection. Funding Sources Supported by NIH 4R00NS114107-03; Klingenstein-Simons Foundation; Whitehall Foundation. Topic Categories Neuroimmunology (NEUR)