Thymus as a target tissue of glucocorticoid action: what are the consequences of glucocorticoids thymectomy?

Glucocorticoids represent the most powerful endogenous anti-inflammatory and immunosuppressive effectors, interfering with virtually every step of immunoinflammatory responses. Glucocorticoids are often the most effective therapy in the prevention or suppression of inflammation and other immunologically mediated processes, but their use is limited by systemic side effects induced by the over-production of reactive oxygen species, causing dysregulation of physiological processes. The thymus is an organ with both endocrine and immune functions. Glucocorticoids induce thymocyte apoptosis, causing a profound reduction in thymic mass and volume and inducing hormonal thymectomy. The clinical aspects of glucocorticoid thymectomy are not under enough investigation. These unwanted systemic side effects may be the consequence of prolonged therapeutic application of glucocorticoids and prolonged or chronic activation of the hypothalamic-pituitary adrenal axis, which may lead to increased and prolonged secretion of glucocorticoids. This review will discuss the metabolic effects of glucocorticoids in the context of thymic physiology asthe primary sex hormone-responsive organ.

Immune system-mediated endothelial damage is associated with NO and antioxidant system disorders.

Two distinct systems of different origin are involved in the pathogenesis of both infectious and immunological vasculitis syndrome: nitric oxide (NO) from endothelial cells and granulocyte NADPH oxidase. In this study, in 31 children with immune system dysfunction, NO, NO synthase (NOS) and antioxidant enzyme activities [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx)], as well as immunological parameters, were investigated. On the basis of the clinical findings, all children were divided into three groups: group I, 8 children clinically showing macular skin manifestations; group II, 11 children with maculo-papulous changes; and group III, 12 children with clinical findings of papulous changes. Plasma NO values in groups II and III were significantly elevated (79.14+/-30.13 and 65.32+/-6.70 micromol/l), compared to the control group (41.24+/-3.65 micromol/l), while group I showed statistically lower values (32.38+/-3.37 micromol/l). In children with the highest level of NO (group II) NOS activity was two-fold higher (1.77+/-0.59 nmol/ml/min; p<0.01) than in controls (0.98+/-0.23 nmol/ml/min). Catalase activity showed a significant increase and SOD activity a significant decrease in all experimental groups, while GPx was not significantly changed. The results show that immune system dysfunction manifested as vasculitis is associated with significant disturbances in the NO system and free radicals scavengers.