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The Molecular and Cellular Mechanisms Responsible for the Anti-inflammatory and Immunosuppressive Effects of Glucocorticoids

  • Chapter
Systemic Corticosteroids for Inflammatory Disorders in Pediatrics

Abstract

Glucocorticoids (GCs) are immunosuppressive agents that inhibit early and late manifestations of acute inflammation and modulate subsequent repair. Therefore, GCs are widely used to treat inflammatory conditions, allergies, and autoimmune diseases. GCs are also prescribed to prevent or treat acute and chronic transplant rejection and graft-versus-host disease.

At clinical doses, the effects of GCs are due to their interactions with several GC receptor (GR) isoforms, which are expressed in nearly all cell types. GRs are located in a multimeric chaperone complex within the cytoplasm or bound to transmembrane receptors, kinases, or other cellular structures. Upon GR activation by a GC, several pathways that promote genomic (gene transcription modulation) and nongenomic (cytoplasmic pathway activation) effects are activated. Genomic effects occur after several minutes and take several hours or days to fully affect cell function. Nongenomic effects manifest rapidly. GR activation modulates a variety of immune and nonimmune cell functions, including extravasation and migration. In particular, GC treatment affects several T-cell subsets, including regulatory T-cell expansion and T helper cell polarization. In addition, when treating infants, the effects of GCs on thymocyte maturation and apoptosis must be considered. In this chapter, the mechanism of GC action, as well as how GCs affect cells of the immune system, is presented and discussed.

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  1. Section of Pharmacology, Department of Medicine, University of Perugia, Building D, 2nd floor, Severi Square 1, San Sisto, Perugia, I-06132, Italy

    Giuseppe Nocentini, Graziella Migliorati & Carlo Riccardi

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  1. Giuseppe Nocentini
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  2. Graziella Migliorati
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  1. AOU Meyer Pediatric Rheumatology, Firenze, Italy

    Rolando Cimaz

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Nocentini, G., Migliorati, G., Riccardi, C. (2015). The Molecular and Cellular Mechanisms Responsible for the Anti-inflammatory and Immunosuppressive Effects of Glucocorticoids. In: Cimaz, R. (eds) Systemic Corticosteroids for Inflammatory Disorders in Pediatrics. Adis, Cham. https://doi.org/10.1007/978-3-319-16056-6_4

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