Exogenous and Endogenous Glucocorticoids in Rheumatic Diseases

Charité University Medicine Berlin and Berlin-Brandenburg Center of Regenerative Therapies, Berlin, Germany.
Arthritis & Rheumatology (Impact Factor: 7.76). 01/2011; 63(1):1-9. DOI: 10.1002/art.30070
Source: PubMed
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Available from: Rainer H Straub, Oct 22, 2014
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    • "Cortisol is an anti-inflammatory hormone on most occasions [111]. Thus, a long-standing increase of serum cortisol levels after acute stressful events such as infectious disease would be unfavorable because of the danger of sepsis. "
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    ABSTRACT: During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases.
    Full-text · Article · Feb 2014 · Arthritis research & therapy
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    • "Glucocorticoids have clinically important anti-inflammatory and immunosuppressive effects which are, among others, used in the treatment of rheumatic diseases [76]. Safety concerns for higher doses or long-term treatment include amongst others glucocorticoids-induced osteoporosis and risk of fracture [77], immunosuppression [78], increased risk of infections, weight gain, leg edema, thinning skin, Cushing's syndrome, hypertension, glaucoma, cataracts, shortness of breath, and sleep disturbances [79], and the onset or worsening of diabetes [80]. "
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    ABSTRACT: The family practitioner plays an important role in the prevention, diagnosis, and early management of chronic pain. He/she is generally the first to be consulted, the one most familiar with the patients and their medical history, and is likely the first to be alerted in case of inadequate pain control or safety and tolerability issues. The family practitioner should therefore be at the center of the multidisciplinary team involved in a patient’s pain management. The most frequent indications associated with chronic pain in family practice are of musculoskeletal origin, and the pain is often multimechanistic. Fixed-dose combination analgesics combine compounds with different mechanisms of action; their broader analgesic spectrum and potentially synergistic analgesic efficacy and improved benefit/risk ratio might thus be useful. A pain specialist meeting held in November 2010 agreed that the fixed-dose combination tramadol/paracetamol might be a useful pharmacological option for chronic pain management in family practice. The combination is effective in a variety of pain conditions with generally good tolerability. Particularly in elderly patients, it might be considered as an alternative to conventional analgesics such as NSAIDs, which should be used rarely with caution in this population.
    Full-text · Article · Apr 2013
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    • "As the mechanisms of action of GCs have become more clear [Buttgereit et al. 2011a], so have the approaches to maximizing beneficial effects (mediated mainly through genomic transrepression ), whilst minimizing unwanted effects (mediated mainly through genomic transactivation). "
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    ABSTRACT: Glucocorticoids (GCs) provide a powerful and widely used anti-inflammatory and disease-modifying therapy for rheumatoid arthritis (RA). However, concerns about adverse effects are driving efforts to find 'safer' GC or GC analogues. One novel approach has been to change the timing of GC delivery, targeting the early hours of the morning to suppress the observed circadian peak in interleukin-6 (IL-6). The CAPRA-1 study has shown that this produces a clinically useful beneficial improvement in morning stiffness and mechanistic studies have shown that this correlates with a strong suppression of the IL-6 early morning peak. With no obvious additional adverse reactions, this improvement in the therapeutic ratio offers additional treatment options in RA, and perhaps in other inflammatory diseases that show circadian variation in symptoms.
    Full-text · Article · Jun 2012 · Therapeutic advances in musculoskeletal disease
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