Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats.
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.
Dimitrijević
M
M
Immunology Research Centre Branislav Janković, Institute of Virology, Vaccines and Sera Torlak, 458 Vojvode Stepe, 11221 Belgrade, Serbia. ilijadim@sezampro.yu
Rauski
A
A
Radojević
K
K
Kosec
D
D
Stanojević
S
S
Pilipović
I
I
Leposavić
G
G
D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000502:physiology / Q000627:therapeutic use; D007124:Immunoenzyme Techniques; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D008297:Male; D010641:Phenotype; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D012710:Serum Albumin, Bovine / Q000276:immunology
D000319:Adrenergic beta-Antagonists; D005938:Glucocorticoids; D012710:Serum Albumin, Bovine; D011433:Propranolol; D003345:Corticosterone