Sympathetic function and markers of inflammation in well-controlled HIV

Abstract

Purpose HIV-associated autonomic neuropathy (HIV-AN) is common and may be associated with both sympathetic and parasympathetic dysfunction. Sympathetic nervous system (SNS) dysfunction occurs on a continuum of hyper-to hypo-adrenergic function, and may be a mediator between psychological stress and chronic inflammation. We sought to describe patterns of SNS dysfunction in people living with HIV, and to determine whether SNS dysfunction is associated with markers of systemic inflammation (focusing on IL-6 and TNF-α) and pain and anxiety. Methods Forty-seven people with well-controlled HIV and without confounding medical conditions or medications completed the Medical Outcomes Survey (MOS-HIV), quantification of a panel of 41 plasma cytokines/chemokines, and a standardized, non-invasive autonomic reflex screen (ARS). Adrenergic baroreflex sensitivity (BRSA) was calculated from the ARS as a measure of SNS function. Results Pain (46%) and anxiety (52%) were commonly reported on the MOS-HIV. BRSA was reduced in 30% of participants and elevated in 9% with the latter occurring only in participants with normal to mild HIV-AN. BRSA was significantly associated with IL-6, but not with TNF-α, pain or anxiety. Exploratory analyses also revealed positive associations of BRSA with numerous other cytokines with no significant inverse associations. Conclusion Higher BRSA, indicative of a more hyperadrenergic state, can be part of the spectrum of early HIV-AN, and may be associated with elevations in multiple cytokines including IL-6. These associations do not appear to be driven by stressors such as pain or anxiety.

A Review of Neurological Symptoms in Long COVID and Clinical Management

“…54 Evidence of persisting changes in both innate and adaptive immunity of people recovered from COVID-19 infection could point to underlying dysregulation of the immune system 55 ; however, other studies have failed to show differences in cytokine profiles between long COVID patients and those who have fully recovered. 56 There is evidence to support chronic states of stress and inflammation triggering autonomic dysfunction, potentially through fluctuations in adrenergic tone, 57 which in turn may perpetuate chronic inflammation through vagal dysfunction and its effects on gastrointestinal function and the microbiome. 58 In the central nervous system (CNS), postmortem neuropathology studies of people deceased from COVID-19 infection have shown evidence of neuroinflammation, microglia activation, hypoxic/ischemic changes, and hemorrhagic or ischemic infarcts.…”

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

“…Catecholamines directly affect the growth and virulence of several species of anaerobes, such as Enterobacteriaceae , in the gut ( 137 , 138 ). More recently, this group demonstrated that higher adrenergic baroreceptor sensitivity, an index of a more hyperadrenergic state, was associated with greater inflammation in PWH ( 139 ). Another study with 4000 PWH from the Strategies for Management of Antiretroviral Therapy study revealed cross-sectional inverse associations between heart rate variability with soluble markers of inflammation and coagulation ( 140 ).…”

Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

“…HIV-1 infects pDC, macrophages and CD4 + T cells in the splenic white pulp, where HIV-1 replicates and then establishes a reservoir of latent virus within these cells during chronic disease [ 85 , 86 , 87 ]. Neural HIV pathology also includes inflammation-mediated destruction of sympathetic nerves that normally regulate the immune functions of these three cell types [ 11 , 31 , 32 ]. As a result, the spleen is a critical site involved in the progression of HIV-1 infection towards clinical immune deficiency and greater susceptibility of infected individuals to opportunistic disease [ 88 , 89 , 90 , 91 ].…”

“…The sympathetic nervous system (SNS) innervates secondary lymphoid organs, and is activated by a variety of stressors, including viral infection [ 9 , 10 ]. Sympathetic dysfunction in HIV-1 infection exists as a continuum of early hyper-to-hypo-adrenergic function with disease progression [ 11 ]. Sympathetic activity is linked to prognostic disease indicators of HIV pathogenesis [ 12 , 13 , 14 , 15 , 16 ], as well as in animal models [ 17 , 18 ].…”

“…More recently, sympathetic hyperactivity, systemic vascular dysfunction and neuropathy have been reported in cART-treated patients with well-controlled HIV-1 infection [ 11 , 31 ]. This finding is associated with an elevation of the proinflammatory cytokine, IL-6, and occurs in the absence of changes in tumor necrosis factor (TNF)-α, pain, or anxiety [ 11 , 32 ]. In an HIV-1 transgenic rat model, HIV-1 induces apoptosis in vascular endothelial cells and splenocytes [ 24 ].…”