β-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats

被引:12
作者
Dimitrijevic, M.
Rauski, A.
Radojevic, K.
Kosec, D.
Stanojevic, S.
Pilipovic, I.
Leposavic, G.
机构
[1] Inst Virol Vaccines & Sera Torlak, Immunol Res Ctr Brainislav Jankovic, Belgrade 11221, Serbia
[2] Fac Pharm, Dept Physiol, Belgrade 11221, Serbia
关键词
adrenalectomy; beta-adrenoceptor blockade; experimental allergic encephalomyelitis; CD4(+)CD25(+) peripheral blood lymphocytes;
D O I
10.1016/j.ejphar.2007.08.021
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:170 / 182
页数:13
相关论文
共 67 条
[1]   The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis [J].
Bauer, J ;
Huitinga, I ;
Zhao, WG ;
Lassmann, H ;
Hickey, WF ;
Dijkstra, CD .
GLIA, 1995, 15 (04) :437-446
[2]   More sympathy for autoimmunity with neuropeptide Y? [J].
Bedoui, S ;
Miyake, S ;
Straub, RH ;
von Hörsten, S ;
Yamamura, T .
TRENDS IN IMMUNOLOGY, 2004, 25 (10) :508-512
[3]  
Berger T, 1997, LAB INVEST, V76, P355
[4]   Catecholaminergic suppression of immunocompetent cells [J].
Bergquist, J ;
Tarkowski, A ;
Ewing, A ;
Ekman, R .
IMMUNOLOGY TODAY, 1998, 19 (12) :562-567
[5]   DISCOVERY OF ENDOGENOUS CATECHOLAMINES IN LYMPHOCYTES AND EVIDENCE FOR CATECHOLAMINE REGULATION OF LYMPHOCYTE FUNCTION VIA AN AUTOCRINE LOOP [J].
BERGQUIST, J ;
TARKOWSKI, A ;
EKMAN, R ;
EWING, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (26) :12912-12916
[6]  
Bergquist J, 2000, ANN NY ACAD SCI, V917, P281
[7]   GLUCOCORTICOID REGULATION OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE (PNMT) IN ORGAN-CULTURE OF SUPERIOR CERVICAL-GANGLIA [J].
BOHN, MC ;
BLOOM, E ;
GOLDSTEIN, M ;
BLACK, IB .
DEVELOPMENTAL BIOLOGY, 1984, 105 (01) :130-136
[8]   CHEMICAL SYMPATHECTOMY AUGMENTS THE SEVERITY OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS [J].
CHELMICKASCHORR, E ;
CHECINSKI, M ;
ARNASON, BGW .
JOURNAL OF NEUROIMMUNOLOGY, 1988, 17 (04) :347-350
[9]   Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3+CD4+CD25+ T regulatory cells in vivo and enhances their capacity to suppress EAE [J].
Chen, Xin ;
Oppenheim, Joost J. ;
Winkler-Pickett, Robin T. ;
Ortaldo, John R. ;
Howard, O. M. Zack .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (08) :2139-2149
[10]   Interferon-γ and interferon-β affect endogenous catecholamines in human peripheral blood mononuclear cells:: Implications for multiple sclerosis [J].
Cosentino, M ;
Zaffaroni, M ;
Ferrari, M ;
Marino, F ;
Bombelli, R ;
Rasini, E ;
Frigo, G ;
Ghezzi, A ;
Comi, G ;
Lecchini, S .
JOURNAL OF NEUROIMMUNOLOGY, 2005, 162 (1-2) :112-121