Expression of β2 adrenoreceptors on peripheral blood mononuclear cells in patients with primary and secondary progressive multiple sclerosis: a longitudinal six month study

Background: β2 Adrenoreceptor expression on peripheral blood mononuclear cells is increased in progressive multiple sclerosis. This increase has been correlated with disease activity in relapsing-remitting multiple sclerosis. Objective: To determine the β2 adrenoreceptor expression in primary and secondary progressive multiple sclerosis in relation to findings on magnetic resonance imaging (MRI) and clinical disease activity. Methods: 10 patients with multiple sclerosis were studied (five with primary progressive and five with secondary progressive forms of the disease) over a period of six months. Monthly clinical and MRI assessments of the brain and spinal cord were carried out. β2 Adrenoreceptor expression was assessed monthly using a ligand binding assay with [125I]iodocyanopindolol. Expression of β2 adrenoceptors on peripheral blood mononuclear cells was also assessed in five normal controls over a similar period. Results: The mean (SEM) value of β2 adrenoreceptor density for the five normal controls was 1346 (183) sites/cell, with affinity Kd of 120 (40) pM. MRI disease activity in primary progressive multiple sclerosis was reported on two occasions and on those occasions the expression of β2 adrenoreceptors was increased in excess of 1900 sites/cell; in the remaining 28 observations β2 adrenoreceptor expression was within the normal range (800 to 1900 sites/cell). In patients with secondary progressive disease, MRI disease activity was observed on 16 occasions. In these patients expression of β2 adrenoreceptors was increased in excess of 2000 sites/cell in all measurements except in one subject who did not show MRI activity throughout the six months period of study. The affinity of the receptors was within the normal range in all cases. Conclusions: Increased expression of β2 adrenoreceptors was correlated with MRI disease activity in two patients with primary progressive multiple sclerosis. In secondary progressive multiple sclerosis, increased expression of β2 adrenoreceptors tended not to correlate with MRI disease activity. This may reflect a persistent Th1 immune reaction in the secondary progressive form of the disease.

[1]  H. Weiner,et al.  Potential of β2-Adrenoceptor Agonists as Add-On Therapy for Multiple Sclerosis , 2002, CNS Drugs.

[2]  H. Weiner,et al.  Oral salbutamol decreases IL-12 in patients with secondary progressive multiple sclerosis , 2001, Journal of Neuroimmunology.

[3]  A. Thompson,et al.  One year follow up study of primary and transitional progressive multiple sclerosis , 2000, Journal of neurology, neurosurgery, and psychiatry.

[4]  D. Arnold,et al.  Heterogeneity of T‐lymphocyte function in primary progressive multiple sclerosis: Relation to magnetic resonance imaging lesion volume , 2000, Annals of neurology.

[5]  X. Montalban,et al.  Immunological profile of patients with primary progressive multiple sclerosis. Expression of adhesion molecules. , 1999, Brain : a journal of neurology.

[6]  G. McDonnell,et al.  Serum soluble adhesion molecules in multiple sclerosis: raised sVCAM-1, sICAM-1 and sE-selectin in primary progressive disease , 1999, Journal of Neurology.

[7]  D. Postma,et al.  Beta-adrenoceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta2-adrenoceptor subtype. , 1998, American journal of respiratory cell and molecular biology.

[8]  E. Vizi,et al.  Stimulation of β-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice , 1998, Journal of Neuroimmunology.

[9]  Khusru Asadullah,et al.  Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury , 1998, Nature Medicine.

[10]  S. Waxman.  Demyelinating diseases--new pathological insights, new therapeutic targets. , 1998, The New England journal of medicine.

[11]  L. Fabbri,et al.  Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12. , 1997, The Journal of clinical investigation.

[12]  A. Thompson,et al.  Longitudinal study of soluble adhesion molecules in multiple sclerosis , 1997, Neurology.

[13]  D. Kasprowicz,et al.  Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help. , 1997, Journal of immunology.

[14]  D. Papanicolaou,et al.  Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. , 1996, Proceedings of the Association of American Physicians.

[15]  Moses Rodriguez,et al.  Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis , 1996, Brain pathology.

[16]  A. Thompson,et al.  Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI. , 1996, Brain : a journal of neurology.

[17]  A. Reder,et al.  Interferon β-1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis , 1996 .

[18]  G. Barker,et al.  MRI dynamics of brain and spinal cord in progressive multiple sclerosis. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[19]  D. Hafler,et al.  Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions , 1995, The Journal of experimental medicine.

[20]  E. Vizi,et al.  Modulation of lipopolysaccharide-induced tumor necrosis factor-α production by selective α- and β-adrenergic drugs in mice , 1995, Journal of Neuroimmunology.

[21]  E. Vizi,et al.  Differential effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice. , 1995, The Journal of endocrinology.

[22]  A. Broocks,et al.  Tumor necrosis factor‐α messenger RNA expression in patients with relapsing‐remitting multiple sclerosis is associated with disease activity , 1995, Annals of neurology.

[23]  C. Mathias,et al.  High β‐adrenoceptor density on peripheral blood mononuclear cells in progressive multiple sclerosis: a manifestation of autonomic dysfunction? , 1994, Acta neurologica Scandinavica.

[24]  A. Thompson,et al.  Increased expression of high affinity IL-2 receptors and beta-adrenoceptors on peripheral blood mononuclear cells is associated with clinical and MRI activity in multiple sclerosis. , 1994, Brain : a journal of neurology.

[25]  A. Thompson,et al.  Spinal cord MRI using multi‐array coils and fast spin echo , 1993, Neurology.

[26]  M. Cuzner,et al.  Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization. , 1993, Cytokine.

[27]  M. Jensen,et al.  Interferon γ- and interleukin-4-secreting cells in multiple sclerosis , 1993, Journal of Neuroimmunology.

[28]  J. Leonard,et al.  β‐Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: A regulatory role for cortisol and interleukin‐1 , 1992 .

[29]  B. Anlar,et al.  Increased lymphocyte beta‐adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28− suppressor cell , 1991, Annals of neurology.

[30]  A. Thompson,et al.  Major differences in the dynamics of primary and secondary progressive multiple sclerosis , 1991, Annals of neurology.

[31]  M. Whalen,et al.  Effects of beta-adrenergic receptor activation, cholera toxin and forskolin on human natural killer cell function. , 1990, The Biochemical journal.

[32]  R. Maselli,et al.  Sympathetic skin responses are decreased and lymphocyte beta‐adrenergic receptors are increased in progressive multiple sclerosis , 1990, Annals of neurology.

[33]  A. Thompson,et al.  Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study. , 1990, BMJ.

[34]  K. Hellstrand,et al.  An immunopharmacological analysis of adrenaline-induced suppression of human natural killer cell cytotoxicity. , 1989, International archives of allergy and applied immunology.

[35]  H. Kirchner,et al.  Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? , 1988, Acta neurologica Scandinavica.

[36]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[37]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[38]  J. Bull,et al.  Institute of Neurology , 1966 .

[39]  Alastair Compston,et al.  McAlpine's Multiple Sclerosis , 2005 .

[40]  H. Weiner,et al.  Potential of beta2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol). , 2002, CNS drugs.

[41]  M. Filippi,et al.  Primary Progressive Multiple Sclerosis , 2002, Topics in Neuroscience.

[42]  S. Merry,et al.  Schizophrenia in children and adolescents: Course and prognosis , 2000 .

[43]  E. Vizi,et al.  Stimulation of beta-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice. , 1998, Journal of neuroimmunology.

[44]  ichard,et al.  AXONAL TRANSECTION IN THE LESIONS OF MULTIPLE SCLEROSIS , 1998 .

[45]  A. Reder,et al.  Interferon beta-1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis. , 1996, Multiple sclerosis.

[46]  E. Vizi,et al.  Differential effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice. , 1995, The Journal of endocrinology.

[47]  M. Jensen,et al.  Interferon gamma- and interleukin-4-secreting cells in multiple sclerosis. , 1993, Journal of neuroimmunology.

[48]  D. McFarlin,et al.  Immunological aspects of demyelinating diseases. , 1992, Annual review of immunology.

[49]  W. Matthews,et al.  McAlpine's multiple sclerosis , 1985 .

[50]  O. Nilsson.  Immunological aspects on demyelinating diseases. , 1972, Acta neurologica Scandinavica. Supplementum.

[51]  A. Bøyum,et al.  Isolation of mononuclear cells and granulocytes from human blood. , 1968 .

[52]  C. Mogensen.  The glomerular permeability determined by dextran clearance using Sephadex gel filtration. , 1968, Scandinavian journal of clinical and laboratory investigation.