β-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats M. Dimitrijević a, ⁎ , A. Rauški a , K. Radojević a , D. Kosec a , S. Stanojević a , I. Pilipović a , G. Leposavić a,b a Immunology Research Centre “Branislav Janković”, Institute of Virology, Vaccines and Sera “Torlak”, 458 Vojvode Stepe, 11221 Belgrade, Serbia b Department of Physiology, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade, Serbia Received 27 March 2007; received in revised form 7 August 2007; accepted 16 August 2007 Available online 23 August 2007 Abstract 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 β-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) β-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) β-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease. © 2007 Elsevier B.V. All rights reserved. Keywords: Adrenalectomy; β-Adrenoceptor blockade; Experimental allergic encephalomyelitis; CD4 + CD25 + peripheral blood lymphocytes 1. Introduction Multiple sclerosis is a chronic disease of the central nervous system characterized by different patterns of inflammation, demyelination and axonal loss (Ewing and Bernard, 1998). Recent findings suggest that the pathogenesis of multiple sclerosis is much more heterogeneous than previously assumed (Prat and Antel, 2005). To understand the pathogenesis of the disease numerous studies have used experimental allergic encephalomy- elitis, a well-established animal model of multiple sclerosis (Tsunoda and Fujinami, 1996). Experimental allergic encephalo- myelitis is an inflammatory disease of the central nervous system that can be induced in genetically susceptible animals through a single immunization with myelin basic protein, encephalitogenic myelin basic protein peptides or other myelin sheath central nervous system antigens in complete Freund's adjuvant. The disease is characterized by mononuclear cell infiltration into the central nervous system causing oedema and demyelination leading to paralysis. MHC class II-restricted CD4 + T cells are Available online at www.sciencedirect.com European Journal of Pharmacology 577 (2007) 170 – 182 www.elsevier.com/locate/ejphar ⁎ Corresponding author. Tel./fax: +381 11 2467 465. E-mail address: ilijadim@sezampro.yu (M. Dimitrijević). 0014-2999/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2007.08.021