The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

Abstract

Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.

Hormonal alterations in PCOS and its influence on bone metabolism

“…Thus, adrenal androgen excess in PCOS is associated with increased inactivation of cortisol by 5β-reductase that may lower cortisol blood levels and stimulate ACTH-dependent steroidogenesis (Gambineri et al 2009). However, the level of inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL1β), which is having an inverse relation with cortisol is found to be elevated in PCOS patients (Coutinho & Chapman 2011). These proinflammatory cytokines are found to be involved in chronic inflammatory bone disease characterized by bone loss around affected joints caused by increased osteoclastic bone resorption (Boyce et al 2005).…”

Neuromyelitis optica spectrum disorder in childhood (a case report)

“…Кортикостероиды оказывают иммуносупрессивный и противовоспалительный эффекты за счет уменьше-ния числа периферических лимфоцитов и провоспали-тельных цитокинов, а также изменения оборота лейко-цитов [5]. Пульс-терапия метилпреднизолоном обычно переносится хорошо, но важно обеспечить пациенту профилактику язвенной болезни желудка и проводить мониторинг общих психиатрических побочных эффек-тов, таких как бессонница и возбуждение.…”

Immuno-radiotherapy for brain metastases

“…Steroids have a wide immunosuppressive action, including reduction of CD8+,CD4+cells and monocyte/neutrophils ratio (depending on the expression of GCR), macrophage dysfunction and T reg induction [10]. Although successful clinical experience would lead to the conclusion that the role of steroids is firmly established in the management of brain metastases, there is a great variability in recommendations and a general lack of well-controlled studies addressing this specific issue.…”