Beta-adrenergic receptor mediated inhibitory control of CD16+ monocyte inflammation is associated with neurobehavioral response to social exclusion and peripheral arterial stiffness a function of HIV.

BACKGROUND: Growing evidence suggests the experience of social exclusion is associated with increased risk for cardiovascular disease (CVD), however the psycho-neuro-immune mechanisms involved remain unclear. Peripheral blood mononuclear cells (PBMCs) play an important role in the etiology of peripheral artery disease. Previous research has uncovered beta-adrenergic receptor inhibitory control (BARIC) of inflammation is blunted in PBMCs from individuals at greater risk for CVD. Chronic HIV disease fits within this paradigm given these individuals living with the virus are more likely to report discrimination and cardiometabolic disease. The current study uses an fMRI task to evaluate whether magnitude of a neural response to the experience of social exclusion is associated with the in-vitro time course of BARIC in CD16+ monocytes in relation to peripheral arterial stiffness.

METHODS: BOLD response to the exclusion versus inclusion trials of a modified Cyberball task were measured in 25 people living with HIV (PWH) (50.8 ± 10.3 yrs) and 19 people living without HIV (PWoH) (52.8 ± 11.9 yrs.). CD16+ monocytes, collected 45 min before, 45 min and 90 min after Cyberball, were isolated using magnetic bead separation (StemCell™) before 18-hr co-stimulation with lipopolysaccharide (LPS) and the non-selective beta-receptor agonist isoproterenol. BARIC was operationalized as the difference in TNF-α expressed by LPS-stimulated CD16+ monocytes without vs. with isoproterenol. A repeated measures ANCOVA assessed whether BOLD response to social exclusion in the subgenual anterior cingulate (sgACC), relates to change in BARIC of TNF-α over the experiment. The interactive effect of HIV+ status and BARIC on peripheral arterial stiffness was evaluated using multiple regression while controlling for age and gender.

RESULTS: Whole-brain analysis revealed sgACC BOLD activation was significantly greater in the sgACC during exclusion compared to inclusion trials surviving FWE small-volume correction (p < 0.05, FWE-SVC). Compared to the middle and highest tercile, individuals within the lowest tercile of sgACC BOLD activation showed BARIC pre-task followed by a post-task decline and recovery of BARIC at 90 min post-task (F(1,32) = 5.741, p = 0.023, η2 = 0.152). Although these neuro-immune associations were not moderated by HIV status, greater BARIC was associated with lower arterial stiffness in PWoH and higher arterial stiffness in PWH (β = -0.89, t = -2.176, p = 0.040).

CONCLUSION: This study supports the role of sgACC in processing social exclusion and relevance of this biobehavioral response to the time course of beta-adrenergic receptor-mediated inhibitory control of TNF-α expression in intermediate and non-classical monocytes and further provides preliminary evidence of paradoxical association between greater BARIC of monocyte inflammation and arterial stiffness in PWH who have not yet developed CVD, however replication in a larger cohort is warranted.