β-Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: A regulatory role for cortisol and interleukin-1

✍ Scribed by Dr Y. Zoukos; J. P. Leonard; T. Thomaides; A. J. Thompson; M. L. Cuzner

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 648 KB
• Volume: 31
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.410310614

✦ Synopsis

An increased density of P-adrenergic receptors was demonstrated on peripheral blood mononuclear cells (PBMCs) from patients with progressive or relapsing-remitting multiple sclerosis (MS). The same observation was made in patients with chronic active rheumatoid arthritis, but not in those with myasthenia gravis. The affinity of the receptors was within the normal range in all tested groups of patients and there was a positive correlation between density and function as determined by intracellular cyclic AMP production after stimulation with isoproterenol. A putative link between inflammatory processes and the functional upregulation of P-adrenergic receptors on PBMCs was tested by in vitro studies with the soluble mediators interleukin-1 and hydrocortisone. A functional upregulation of P-adrenergic receptors was observed when PBMCs from normal control subjects were cultured in the presence of either mediator, whereas the already upregulated receptor density on PBMCs from patients with MS remained unchanged. Whether this represents a recovery mechanism to inflammation in MS or a blunting of homeostatic immunoregulatory mechanisms requires further investigation. Zoukos Y , Leonard JP, Thomaides T, Thompson AJ, Cuzner ML. P-Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: a regulatory role for cortisol and interleukin-1. Ann Neurol 1992;31:657-662 Multiple sclerosis (MS) is a primary demyelinating disease characterized by spontaneous relapses and remissions, the triggers of which are unknown. Immunoregulatory mechanisms may contribute, involving interactions among the immune, neural, and endocrine systems. Bidirectional interactions are evinced through the hypothalamic-pituitary-adrenal axis [ 11, lymphocyte neurotransmitter receptors [2, 31, and sympathetic innervation of lymphoid tissue [4, 51. Changes in neural and endocrine parameters, known to exert feedback control on immunological reactivity, have been observed during the preclinical and clinical stages of both primary acute and adoptively transferred experimental autoimmune encephalomyelitis (EAE) [b, 71.

Furthermore clinical disease is exacerbated in sympathectomized as well as adrenalectomized animals IS,

An increased density of P-adrenergic receptors on splenic lymphocytes has been observed in EAE when immunoproliferative responses are most marked [b, 71. An increased density of P-adrenergic receptors on circulating lymphocytes has also been reported in progressive MS, which has been ascribed to autonomic abnormalities [lo]. As lymphocyte functions are altered by the stimulation of P-adrenergic receptors Ill}, which are themselves regulated by a range of cytokines and growth factors [12), we reexamined the density of P-adrenergic receptors on circulating lymphocytes in conjunction with measuring plasma cortisol, noradrenaline (NA), and adrenaline (Ad) levels in patients with different clinical categories of MS and investigated in vitro the effects of steroids and the cytokine interleukinla (IL-ICY) on P-adrenergic receptor density and function.