Massage-like stroking boosts the immune system in mice

Recent clinical evidence suggests that the therapeutic effect of massage involves the immune system and that this can be exploited as an adjunct therapy together with standard drug-based approaches. In this study, we investigated the mechanisms behind these effects exploring the immunomodulatory function of stroking as a surrogate of massage-like therapy in mice. C57/BL6 mice were stroked daily for 8 days either with a soft brush or directly with a gloved hand and then analysed for differences in their immune repertoire compared to control non-stroked mice. Our results show that hand-but not brush-stroked mice demonstrated a significant increase in thymic and splenic T cell number (p lt 0.05; p lt 0.01). These effects were not associated with significant changes in CD4/CD8 lineage commitment or activation profile. The boosting effects on T cell repertoire of massage-like therapy were associated with a decreased noradrenergic innervation of lymphoid organs and counteracted the immunosuppressive effect of hydrocortisone in vivo. Together our results in mice support the hypothesis that massage-like therapies might be of therapeutic value in the treatment of immunodeficiencies and related disorders and suggest a reduction of the inhibitory noradrenergic tone in lymphoid organs as one of the possible explanations for their immunomodulatory function

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P lt 0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P lt 0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P lt 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis

Chronic a1-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation

In order to examine the influence of chronic a1-adrenergic receptor (a1-AR) blockade on the thymus structure and T-cell maturation, peripubertal and adult male rats were treated with urapidil (0.20 mg/kg BW/d; s.c.) over 15 consecutive days. Thymic structure and phenotypic characteristics of the thymocytes were assessed by stereological and flow cytometry analysis, respectively. In immature rats, treatment with urapidil reduced the body weight gain and, affecting the volume of cortical compartment and its cellularity decreased the organ size and the total number of thymocytes compared to age-matched saline-injected controls. The percentage of CD4+8- single positive (SP) thymocytes was decreased, while that of CD4-8+ was increased suggesting, most likely, a disregulation in final steps of the positively selected cells maturation. However, a1- AR blockade in adult rats increased the thymus weight as a consequence of increase in the cortical size and cellularity. The increased percentage of most immature CD4-8- double negative (DN) cells associated with decreased percentage of immature CD4+8+ double positive (DP) thymocytes suggests a decelerated transition from DN to DP stage of T-cell development. As in immature rats, the treatment in adult rats evoked changes in the relative numbers of SP cells, but contrary to immature animals, favoring the maturation of CD4+8- over CD4-8+ thymocytes. These results demonstrate that: i) chronic blockade of a1-ARs affects both the thymus structure and thymocyte differentiation, ii) these effects are age-dependent, pointing out to pharmacological manipulation of a1-AR-mediated signaling as potential means for modulation of the intrathymic T-cell maturation

Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis

There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually diergic changes in thymopoietic efficiency, which in rodents occur around puberty and lead to a substantial phenotypic and functional remodeling of the peripheral T-cell compartment. This in turn leads to an alteration in the susceptibility to infection and various immunologically mediated pathologies. Our laboratory has explored interdependence in the programming and development of the hypothalamo-pituitary-gonadal axis and thymus using experimental model of neonatal androgenization. We have outlined critical points in the complex process of T-cell development depending on neonatal androgen imprinting and the peripheral outcome of these changes and have pointed to underlying mechanisms. Our research has particularly contributed to an understanding of the putative role of changes in catecholamine-mediated communications in the thymopoietic alterations in adult neonatally androgenized rats

End-point effector stress mediators in neuroimmune interactions: their role in immune system homeostasis and autoimmune pathology

Much evidence has identified a direct anatomical and functional link between the brain and the immune system, with glucocorticoids (GCs), catecholamines (CAs), and neuropeptide Y (NPY) as its end-point mediators. This suggests the important role of these mediators in immune system homeostasis and the pathogenesis of inflammatory autoimmune diseases. However, although it is clear that these mediators can modulate lymphocyte maturation and the activity of distinct immune cell types, their putative role in the pathogenesis of autoimmune disease is not yet completely understood. We have contributed to this field by discovering the influence of CAs and GCs on fine-tuning thymocyte negative selection and, in particular, by pointing to the putative CA-mediated mechanisms underlying this influence. Furthermore, we have shown that CAs are implicated in the regulation of regulatory T-cell development in the thymus. Moreover, our investigations related to macrophage biology emphasize the complex interaction between GCs, CAs and NPY in the modulation of macrophage functions and their putative significance for the pathogenesis of autoimmune inflammatory diseases

Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes

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