Sympathetic Abnormalities during Autoimmune Processes

Abstract

The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions. Disturbances in these interactions are likely to have consequences during lymphoproliferative diseases. Work derived from our group as well as from several others led us to the hypothesis that the overstimulation of the immune system that characterizes this type of pathology results in decreased sympathetic nerve activity in lymphoid organs. To explore this possibility, we used as a model lpr/lpr mice, which develop a genetically determined autoimmune, lupus-like lymphoproliferative disease. We show that 18-week-old female C57Bl/6J lpr/lpr mice, which do not show overt symptoms of the disease but already have increased IgM and IgG2a levels in the blood, have decreased noradrenaline (NA) concentration and content in the spleen, but not in the kidney, as compared to normal C57Bl/6J littermates. Lpr/lpr mice do not express normal Fas, and therefore apoptosis cannot be triggered through this receptor. The defects in sympathetic innervation in the spleen of lpr/lpr mice prompted us to evaluate whether NA could influence lymphoid cell mass by inducing apoptosis. We found that NA can directly induce apoptosis in normal lymphoid cells via beta-adrenergic receptors. From the reported results we propose that reduction in sympathetic nerve function in lpr/lpr mice contributes to aggravation of the disease and suggest that in addition to the incapacity to mount Fas-mediated apoptosis, a second proapoptotic mechanism, namely, that triggered by NA, is defective in these animals because of reduced availability of the neurotransmitter.

Social Defeat Modulates T Helper Cell Percentages in Stress Susceptible and Resilient Mice

“…A decrease in T cell numbers or percentages has been reported before in various animal models of acute and chronic stress [49,50,51,52]. Stress exposure results in an enhanced release of glucocorticoids and catecholamines that may induce apoptosis in peripheral T cells [53,54]. Enhanced T cell apoptosis following stressful events has further been attributed to lack of tryptophan, an essential factor in T cell proliferation [55].…”

Preponderance of sensory versus sympathetic nerve fibers and increased cellularity in the infrapatellar fat pad in anterior knee pain patients after primary arthroplasty

“…The sympathetic nervous system confers direct anti-inflammatory and pro-apoptotic effects when concentrations of neurotransmitters are in the range of 10 À6 to 10 À5 M via the b-adrenergic receptor on target cells. [28][29][30][31][32][33][34][35][36][37] High concentrations of norepinephrine can appear in the vicinity of sympathetic nerve terminals. 38 In addition to norepinephrine, endogenous opioids such as methi-onine enkephalin and leucine enkephalin are released from sympathetic nerve terminals, and these opioids block release of substance P from sensory nerve fibers in the bidirectional crosstalk.…”

Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)?

“…IMIDs induce sympathetic nerve pathology in the secondary lymphoid organs including the spleen, the lymph nodes that drain targeted sites of inflammation, and disease-targeted sites of chronic inflammation. For example, we and others have reported sympathetic neuropathy in the spleen and affected joints in murine models of lupus [ 90 , 132 , 133 , 134 ]. In humans, high SNA and/or sympathetic neuropathy are evident in diabetes [ 47 ], hypertension [ 47 ], heart failure, and COPD [ 135 , 136 ].…”