More MS news articles for Nov 2001

Stress, glucocorticoids and the susceptibility to develop autoimmune disorders of the central nervous system

Neurological Sciences
Abstract Volume 22 Issue 2 (2001) pp 159-162
C. Morale (1), J. Brouwer (2), N. Testa (1), C. Tirolo (1), N. Barden (3), C. D. Dijkstra (2), S. Amor (4), B. Marchetti (5)
(1) Neuropharmacology Unit, OASI (IRCCS), Institute for Research and Care on Mental Retardation and Brain Aging, Troina (EN), Italy
(2) Molecular Cell Biology and Immunology, Vrije Universiteit, 1081 BT, Amsterdam, The Netherlands
(3) CHUL Research Centre and Department of Anatomy and Physiology, Laval University, Quebec, Canada, G1V 4G2
(4) Department of Neuroinflammation, Division of Neurosciences, Imperial College, School of Medicine, Charing Cross Campus, London, UK
(5) Department of Pharmacology, Medical School, University of Sassari, I-07100 Sassari, Italy and Neuropharmacology Unit, OASI (IRCCS) Institute for Research and Care on Mental Retardation and Brain Aging, I-94018 Troina (EN), Italy


Alterations of the immunoendocrine circuit along the hypothalamic-pituitary-adrenocortical (HPA) axis in various autoimmune diseases have recently been observed, suggesting a modulatory role of this feedback regulation in the pathogenesis of autoimmune diseases.

Susceptibility to experimental autoimmune encephalomyelitis (EAE) may be influenced by variations in the production of endogenous glucocorticoid hormones (GC).

The adrenocortical response is central to recovery from EAE in the Lewis rat, as reflected by increased severity of the disease in adrenalectomized animals.

The key role of GC in modifying the induction and progression of EAE is also emphasized by a reversal of corticoid-mediated effects through treatment with glucocorticoid receptor (GR) antagonists.

We studied the relationship between defective GR function and susceptibility to EAE in transgenic (Tg) mice expressing GR antisense RNA.

EAE was induced with the encephalitogenic myelin oligodendrocyte peptide (pMOG 36-50) in wild type (Wt) and transgenic (Tg) female mice bearing GR antisense RNA.

pMOG 36-50 induced typical EAE in Wt mice but not in Tg mice.

Histological examination of brains and spinal cords of Wt mice showed the presence of inflammation and/or demyelination, whereas in Tg mice neither were present.

Although the mechanisms underlying the resistance of Tg mice to EAE induction are not yet clarified, compensatory changes at different levels of the HPA-immune axis in response to the potent immunogenic challenge are likely to participate in the observed effects.

This work underlies the plasticity of the HPA-immune axis and suggests that pharmacological manipulation of neuroendocrine-immune networks may be a therapy of multiple sclerosis.

© Springer-Verlag Italia 2001