Increased lymphocyte beta‐adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28− suppressor cell

Karaszewski, Joseph W.; Reder, Anthony T.; Anlar, Banu; Kim, Woo Chan; Arnason, Barry G. W.

doi:10.1002/ana.410300109

Cited by 65 publications

(40 citation statements)

References 31 publications

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“…Similarly, in the MRL-lpr/lpr mouse, a genetic model of the human autoimmune disease systemic lupus erythematosus, noradrenergic innervation and noradrenaline content were reduced in the spleen prior to the onset of observed splenomegaly and remained reduced at all ages examined [49]. In MS patients, increased β-adrenergic receptor density on PBMCs, including lymphocytes, has been well documented [50][51][52][53][54][55]. This increase in β-adrenoreceptor density has been shown to be correlated with the expression of high affinity IL-2 receptors (IL-2R) on PBMCs and disease activity of RRMS.…”

Section: Adrenergic Receptorsmentioning

confidence: 89%

G protein-coupled receptors as therapeutic targets for multiple sclerosis

Xie

2012

Cell Res

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G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spectrum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or pharmacological manipulations. Hopefully some of these findings will lead to the development of novel therapies for MS in the near future.

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Section: Adrenergic Receptorsmentioning

confidence: 89%

G protein-coupled receptors as therapeutic targets for multiple sclerosis

Xie

2012

Cell Res

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“…in vitro [13,41], animal [5,14,39], and clinical studies [4]. Autonomic dysfunction may be a feature not only of the disease but also due to any one of several pathogenetic factors.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance

Flachenecker¹,

Wolf²,

Krauser³

et al. 1999

Journal of Neurology

101

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Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS), but clinical studies disagree on the frequency and type of abnormalities in autonomic function tests. Orthostatic dizziness (OD) has been reported in up to 49% of patients, but the pathophysiological mechanisms are poorly understood. This study investigated cardiovascular reflex tests and their association with OD in patients with MS in order to examine the hypothesis that the sympathetic nervous system is specifically involved in these patients. Forty patients with clinically active relapsing-remitting (n = 27) and secondary progressive MS (n = 13), aged 35.0+/-8.5 years, were studied by parasympathetic (heart rate responses to the Valsalva maneuver, deep breathing, and active change in posture) and sympathetic function tests (blood pressure responses to active change in posture and sustained handgrip), and by spectral analysis of heart rate variability during rest and during standing. Results were compared to those obtained in 24 healthy volunteers, aged 29.4+/-7.2 years. A standardized questionnaire was used to evaluate symptoms of orthostatic intolerance. Abnormal responses on at least one cardiovascular reflex test were observed in 40% of MS patients, compared to 17% of the control group, with a statistically significant involvement of the sympathetic vasomotor system. Orthostatic intolerance was reported in 50% of patients (controls: 14%, P<0.006). Subgroup comparison of patients with and without OD suggests that orthostatic intolerance results from impaired sympathetic vasoconstriction. These results provide further evidence that the sympathetic nervous system is involved in patients with MS.

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“…These findings were confirmed by another study showing that B lymphocytes had the greatest number of b-ARs with 12.1 AE 1.8 fmol/10 6 cells, followed by CD8+ T lymphocytes with 3.4 AE 0.4 fmol/10 6 and CD4+ T lymphocytes with 1.2 AE 0.1 fmol/10 6 cells (Karaszewski et al 1990). In another study, the same authors reported 2.8 AE 0.3 fmol/10 6 cells in CD8+CD28-(suppressor) T cells versus 1.4 AE 0.4 fmol/10 6 cells in CD8+CD28+ (cytotoxic) T cells (Karaszewski et al 1991).…”

Section: T and B Lymphocytesmentioning

confidence: 91%