- Meeting abstract
- Open access
- Published:
Why and how to optimize glucocorticoid treatment in rheumatoid arthritis
Arthritis Research & Therapy volume 14, Article number: A19 (2012)
Glucocorticoids (GC) are the most potent anti-inflammatory and immunosuppressive hormones mainly produced by the adrenal glands in humans.
The central nervous clock system, under the influence of light/dark alternation, "creates" the internal circadian rhythms and the organisms by "feeling" these rhythmic external changes, synchronize their physical activities, including sleep, related nocturnal hormone synthesis and immune function [1].
As a matter of fact, GC rise during the night around 3 am and start to exert anti-inflammatory and immunosuppressive activities. On the other hand, the nocturnal pineal hormone melatonin, that rises earlier in the night with darkness, has been linked to chronic inflammation since at normal to slightly elevated concentrations stimulate many aspects of the immune/inflammatory response, especially at the level of macrophages [2].
The immune-supportive role of melatonin and the reduced immune suppression linked to decreased endogenous GC (due to the chronic stress of the disease) have been delineated in the context of the circadian rhythms of immune/inflammatory reaction and related clinical (morning) symptoms, at least in RA [3].
Therefore, the most advanced approach to optimize the risk-benefit ratio of long-term low-dose GC treatment is the GC-chronotherapy, using a modified release (MR) prednisone (release during the night) and following the circadian rhythms.
In fact in RA, the circadian rhythms of clinical symptoms are more evident in the early morning hours, since preceded by nocturnal elevated levels of pro-inflammatory cytokines (i.e.IL-6). Therefore, since prevention of nocturnal rise of pro-inflammatory cytokines by GC therapy would be more effective than treating established symptoms in the morning and might reduce doses and side effects, a MR prednisone was developed, which releases prednisone approximately four hours after ingestion (i.e., at approximately 2-3 am when taken at bedtime) [4]. In addition to all recognized therapeutic effects obtained with conventional prednisone, MR prednisone was shown to have similar profile of adverse effects but without additional suppression of hypothalamic-pituitary-adrenal (HPA) axis [5].
In conclusion, night-time low dose long-term GC therapy in chronic rheumatic diseases such as RA, is today considered as an "hormonal replacement therapy" that optimally implement the peripheral insufficiency of endogenous GC in modulating the immune/inflammatory reaction.
References
Cutolo M: Rheumatoid arthritis: circadian and circannual rhythms in RA. Nat Rev Rheumatol. 2011, 7: 500-502. 10.1038/nrrheum.2011.115.
Cutolo M, Maestroni GJ: The melatonin-cytokine connection in rheumatoid arthritis. Ann Rheum Dis. 2005, 64: 1109-1111. 10.1136/ard.2005.038588.
Cutolo M, Straub RH, Buttgereit F: Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside. Ann Rheum Dis. 2008, 6: 905-908.
Buttgereit F, Doering G, Schaeffler A, et al: Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet. 2008, 371: 205-214. 10.1016/S0140-6736(08)60132-4.
Alten R, Doring G, Cutolo M, et al: Hypothalamus-pituitary-adrenal axis function in patients with rheumatoid arthritis treated with nighttime-release prednisone. J Rheumatol. 2010, 37: 2025-2031. 10.3899/jrheum.100051.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Cutolo, M. Why and how to optimize glucocorticoid treatment in rheumatoid arthritis. Arthritis Res Ther 14 (Suppl 2), A19 (2012). https://doi.org/10.1186/ar3726
Published:
DOI: https://doi.org/10.1186/ar3726