Analyses of similarities and differences in glucocorticoid therapy between rheumatoid arthritis and ankylosing spondylitis - a systematic comparison.
Glucocorticoids (GCs) have powerful and potent anti-inflammatory and immunomodulatory effects and are widely established in regard to the treatment of rheumatism and other diseases. In rheumatoid arthritis (RA), GCs are used systemically at several different dosages and/or local (intraarticular) therapy. They have been shown to exert strong short-term anti-inflammatory effects but also long-term positive effects on radiographic progression of the disease. In comparison, patients with ankylosing spondylitis (AS) are considered to be less responsive to GC therapy than patients with RA, although controlled studies on the effects of low-dose GCs in AS are lacking. In AS, GCs are mainly used for local therapy and occasionally for systemic pulse therapy only. The underlying mechanisms for these differences are unclear. GCs act on primary and secondary immune cells via different mechanisms of action: cytosolic GC receptor (cGCR)-mediated genomic and non-genomic effects, membrane-bound GC receptor (mGCR)-mediated non-genomic effects and - as achieved at very high concentrations - non-specific non-genomic effects. The phenomenon of GC resistance is also known in RA. Several different mechanisms may mediate this phenomenon; among them are alterations in number, binding affinity or phosphorylation status of the GCR, polymorphic changes and/or over-expression of chaperones/ co-chaperones, increased expression of inflammatory transcription factors, the multidrug resistance pump, over-expression of the GCR beta isoform, alteration in the expression of mGCR and imbalance of 11beta-hydroxysteroid dehydrogenase type 1 & 2 activity. Translation of insights on GC action and resistance obtained in RA to AS may contribute to a better understanding of the pathophysiology of both diseases.
Spies
C M
CM
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany. cornelia.spies@charite.de
Burmester
G-R
GR
Buttgereit
F
F
D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001175:Arthrography; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000187:drug effects; D007270:Injections, Intra-Articular; D020551:Pulse Therapy, Drug; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D018501:Antirheumatic Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid