Clinical Use and Molecular Action of Corticosteroids in the Pediatric Age

Abstract

Corticosteroids are the mainstay of therapy for many pediatric disorders and sometimes are life-saving. Both endogenous and synthetic derivatives diffuse across the cell membrane and, by binding to their cognate glucocorticoid receptor, modulate a variety of physiological functions, such as glucose metabolism, immune homeostasis, organ development, and the endocrine system. However, despite their proved and known efficacy, corticosteroids show a lot of side effects, among which growth retardation is of particular concern and specific for pediatric age. The aim of this review is to discuss the mechanism of action of corticosteroids, and how their genomic effects have both beneficial and adverse consequences. We will focus on the use of corticosteroids in different pediatric subspecialties and most common diseases, analyzing the most recent evidence.

Short-Term Therapeutic Effects of Topical Corticosteroids on Refractory Dry Eye Disease: Clinical Usefulness of Matrix Metalloproteinase 9 Testing as a Response Prediction Marker

“…The therapeutic effects of corticosteroids are mediated by the transactivation and transrepression of gene transcription via the glucocorticoid receptor, and most immune cells are affected by corticosteroids. 30 , 31 corticosteroids attenuates the innate immune response by inhibiting the activation and differentiation of APCs and reducing the secretion of pro-inflammatory cytokines. Additionally, corticosteroids reduce the activation of neutrophil and B cell, and modulate T cell polarization and apoptosis.…”

“…Additionally, corticosteroids reduce the activation of neutrophil and B cell, and modulate T cell polarization and apoptosis. 30 , 31 These anti-inflammatory activities of corticosteroids are mediated via its interactions with numerous molecules involved in intracellular signaling transduction, including JNK, STAT, MAPK, NF-kB, and guanine nucleotide-binding proteins (G proteins). 30 , 31 The exposure of epithelial cells in the ocular surface to desiccating stress also activates several signal transduction molecules, and elevates the levels of proinflammatory cytokines, chemokines, and MMPs.…”

“… 30 , 31 These anti-inflammatory activities of corticosteroids are mediated via its interactions with numerous molecules involved in intracellular signaling transduction, including JNK, STAT, MAPK, NF-kB, and guanine nucleotide-binding proteins (G proteins). 30 , 31 The exposure of epithelial cells in the ocular surface to desiccating stress also activates several signal transduction molecules, and elevates the levels of proinflammatory cytokines, chemokines, and MMPs. 15 , 32 These mediators promote the maturation of APCs, and the APCs trigger the expansion of the helper T cell subtypes 1 and 17 (afferent arm activation).…”

Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis—A Critical Review of Its Pathogenesis and Treatment

“…Downregulation of these pathways results in a decrease in the release of many pro-inflammatory cytokines (IL-1β, TNF-α, IL-6 and multiple other interleukins) (146), as well as, inhibit co-stimulatory molecules involved in the activation and differentiation of neutrophils, antigen-presenting cells, and lymphocytes (147). Corticosteroids also affect somatic and endothelial cells by downregulating adhesion molecules, and accumulation of neutrophils (148), inhibits platelet adherence (149) and activities of T and B lymphocytes (148). Initially, intravenous methylprednisolone is preferred, particularly during cytokine storm, and can be slowly transitioned and tapered to daily oral prednisone.…”

Safety and Efficacy Evaluation of Traditional Chinese Medicine (Qingre‐Lishi‐Yishen Formula) Based on Treatment of Regular Glucocorticoid Combined with Cyclophosphamide Pulse in Children Suffered from Moderately Severe Henoch–Schonlein Purpura Nephritis with Nephrotic Proteinuria

“…Furthermore, the immunosuppressant usage may exert therapeutic effect but may also be blamed for severe adverse events both in the short-term and in the long-term. As to glucocorticoid, use of high-doses for a long time may lead to Cushing's syndrome (moon face, weight gain, and centripetal redistribution of fat), secondary diabetes mellitus, hypertension, dyslipidemia, and ocular complication and prone to infections [8]. Cyclophosphamide is one of the most commonly used alkylating agents, which can exert immunosuppressive function by causing cytotoxic and antiproliferative effects on various immune cells.…”