Mitogenic response and steroid sensitivity in MS lymphocytes

Wei, T; Knight, Richard; Lightman, Stafford

doi:10.1111/j.1600-0404.1997.tb00234.x

Cited by 7 publications

(1 citation statement)

References 29 publications

(18 reference statements)

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“…However, conflicting results are reported by studies investigating in vitro GC resistance in MS. Whereas some have demonstrated reduced sensitivity of patients' white blood cells to GC treatment in order to suppress lymphocyte function [223], others have found no differences [224] as compared to healthy controls. Observations of reduced GC sensitivity have been made in other autoimmune diseases or inflammatory diseases, including RA and asthma [225, 226], and several factors have been identified contributing to GC resistance, such as reduced GR expression [227].…”

Section: Intervening With the Neuroendocrine Immune System For Trementioning

confidence: 99%

Neuroendocrine Immunoregulation in Multiple Sclerosis

Deckx

Lee

Berneman

et al. 2013

Clinical and Developmental Immunology

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Currently, it is generally accepted that multiple sclerosis (MS) is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

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Section: Intervening With the Neuroendocrine Immune System For Trementioning

confidence: 99%

Neuroendocrine Immunoregulation in Multiple Sclerosis

Deckx

Lee

Berneman

et al. 2013

Clinical and Developmental Immunology

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Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis

Bergh

Grasser

Trenkwalder

et al. 1999

Journal of Neurology

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Although the exact etiology of multiple sclerosis (MS) remains unresolved, immune reactions are believed to be the central pathogenic mechanisms. Endogenous and therapeutic steroid hormones affect the immune system, and inflammatory diseases are associated with activation of the hypothalamic-pituitary-adrenal axis, providing evidence of an immune-endocrine interplay. Function tests in MS have revealed dysregulation of the hypothalamic-pituitary-adrenal system in a substantial proportion of patients. We characterized glucocorticoid receptor (GR) binding in peripheral blood lymphocytes from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity, using a whole-cell binding assay with [3H]dexamethasone as the ligand. GR binding parameters did not differ significantly between patients (Kd 8.98 +/- 1.07 nM, Bmax 183 +/- 29.8 fmol/mg) and controls (Kd 9.36 +/- 1.17 nM, Bmax 158 +/- 16 fmol/mg). No effect of age, sex, course, duration or severity of disease, or prior steroid treatments was detected. GR binding parameters were analyzed in relation to the results of the combined dexamethasone-CRH test, which reflects corticosteroid receptor function at the hypothalamus, in 30 patients and 9 controls. While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level, the patients did not. These data suggest that the physiological relationship between binding and function of the glucocorticoid receptor is disturbed in MS.

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