The study revealed that beta-adrenoceptor blockade with propranolol (0.40 mg/100 g/day, s.c.) in adult male DA rats: (i) increased the thymocyte proliferation and apoptosis, (ii) caused disturbances in kinetics of T cell differentiation leading to distinguishable changes in relative proportion of thymocytes at distinct maturational steps and to an expansion of the most mature single positive (CD4+, CD8+) thymocyte pool, (iii) affected the relative proportion of neither CD4+ nor CD8+ peripheral blood lymphocytes (PBL), and (iv) augmented the relative number of CD8+CD25+ cells. Thus, the results suggest the role of beta-adrenoceptors in fine-tuning of T cell maturation, and, possibly, distribution and activation of distinct PBL subsets.
"Rats were treated with propranolol hydrochloride (0.40 mg/ 100 g body weight /day) for 4 or 16 days starting 3 days prior to the induction of experimental allergic encephalomyelitis (day 0). The dose was chosen on the basis of our previous results that indicated that propranolol effectively modulated T-cell maturation and phenotypic characteristics of peripheral blood lymphocytes from Dark Agouti rats (Rauški et al., 2003). "
[Show abstract][Hide abstract] 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 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.
European Journal of Pharmacology 01/2008; 577(1-3):170-82. DOI:10.1016/j.ejphar.2007.08.021 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Host defense against pathogens is regulated by cross-talk between two major adaptive systems of the body—the nervous and immune systems. This bidirectional communication is essential for maintaining homeostasis. Sympathetic nerves that innervate lymphoid tissues provide one of the major outflows from the brain to regulate tissue repair and host defense. This review focuses on the role of (sympathetic nervous system) SNS in neuroimmune regulation, an area that has received much less attention than the other major immunoregulatory pathway, the hypothalamo–pituitary–adrenal (HPA) axis. Research over the past 25 years has demonstrated that norepinephrine (NE) fulfills the criteria for neurotransmission in lymphoid tissue, with both primary and secondary immune organs receiving an extensive supply of sympathetic nerves that directly contact with immunocytes. Under stimulation, NE released from terminals in secondary lymphoid organs interacts with adrenergic receptors (AR) expressed on immune cells to affect the development, trafficking, circulation, proliferation, cytokine production, and the functional activity of variety of lymphoid and myeloid cells. Our knowledge of the role of sympathetic nerves in modulating hematopoietic functions of primary lymphoid organs (bone marrow and thymus) and mucosal immunity are extremely limited. While the immune system is not absolutely dependent upon signals from the brain to function, sympathetic-immune modulation may drive host defense toward protection against, or progression toward, immune-related diseases. Additionally, signals from the (SNS) may enhance immune readiness during disease- or injury-induced ‘fight-or-flight’ responses. A better understanding of neural–immune interactions may foster the development of strategies for treating immune-mediated diseases, particularly where neuroimmune cross-talk may be dysregulated.
Clinical Neuroscience Research 08/2006; 6(1-6):3-33. DOI:10.1016/j.cnr.2006.04.003 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of beta-adrenoceptors (beta-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCRalphabeta(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCRalphabeta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.
International Immunopharmacology 06/2007; 7(5):674-86. DOI:10.1016/j.intimp.2007.01.017 · 2.47 Impact Factor
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