Exogenous and endogenous glucocorticoids in rheumatic diseases

Buttgereit, Frank; Burmester, Gerd‐Rüdiger; Straub, Rainer H.; Seibel, Markus J.; Zhou, Hong

doi:10.1002/art.30070

Cited by 88 publications

(53 citation statements)

References 59 publications

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“…Adverse effects of therapy include steroid myopathy, nosocomial infection, aseptic bone necrosis, accelerated osteoporosis, weight gain, metabolic derangements, and Cushingoid appearance (35,36). In addition to these side effects, if steroid therapy fails, a patient may need to undergo surgery or systemic B-cell depletion with monoclonal antibodies or cytotoxic drugs, with side effects of severe infection, antibody transfusion reactions, and even the development of malignancies (10,37).…”

Section: Discussionmentioning

confidence: 99%

Clearance of pathological antibodies using biomimetic nanoparticles

Copp¹,

Fang²,

Luk³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

248

183

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Pathological antibodies have been demonstrated to play a key role in type II immune hypersensitivity reactions, resulting in the destruction of healthy tissues and leading to considerable morbidity for the patient. Unfortunately, current treatments present significant iatrogenic risk while still falling short for many patients in achieving clinical remission. In the present work, we explored the capability of target cell membrane-coated nanoparticles to abrogate the effect of pathological antibodies in an effort to minimize disease burden, without the need for drug-based immune suppression. Inspired by antibody-driven pathology, we used intact RBC membranes stabilized by biodegradable polymeric nanoparticle cores to serve as an alternative target for pathological antibodies in an antibody-induced anemia disease model. Through both in vitro and in vivo studies, we demonstrated efficacy of RBC membrane-cloaked nanoparticles to bind and neutralize anti-RBC polyclonal IgG effectively, and thus preserve circulating RBCs.nanomedicine | immune therapy | type II hypersensitivity reaction | autoantibody

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Section: Discussionmentioning

confidence: 99%

Clearance of pathological antibodies using biomimetic nanoparticles

Copp¹,

Fang²,

Luk³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

248

183

View full text Add to dashboard Cite

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“…These findings point to an important role of the glucocorticoid receptor in the effects of dexamethasone and are consistent with the findings of many studies on the mechanisms of glucocorticoid-induced immunosuppression. Even though the inhibitory actions of RU486 are complicated, the results of these studies are clear (5).…”

Section: Discussionmentioning

confidence: 99%

“…We have used poly(I:C) as a model for immune stimulation since prior studies have demonstrated its effectiveness in inducing MP release by macrophages and since this compound can mimic the effects of viral double-stranded RNA (13). For a comparison of the effects of estradiol and progesterone, we have studied dexamethasone as a model for a glucocorticoid (5,36). We have also investigated the potential role of receptors in these responses by characterizing the effects of RU486.…”

mentioning

confidence: 99%

Effects of Progesterone and Estradiol Sex Hormones on the Release of Microparticles by RAW 264.7 Macrophages Stimulated by Poly(I:C)

Pisetsky

Spencer

2011

Clin. Vaccine Immunol.

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Microparticles (MPs) are small membrane-bound vesicles that display proinflammatory and prothrombotic properties. These particles can be released by macrophages stimulated by ligands of the Toll-like receptors (TLRs) in a process that depends on nitric oxide (NO) production. Since sex hormones can modulate macrophage responses, we investigated the effects of progesterone and estradiol on macrophage particle release in vitro, comparing the responses with those induced by the glucocorticoid dexamethasone. As a model system for particle release, RAW 264.7 cells were stimulated in vitro with poly(I:C), a ligand of TLR3. Microparticles were measured by flow cytometry, while NO was measured by the Griess reaction. As the results of these studies showed, progesterone but not estradiol can block particle release by RAW264.7 cells treated with poly(I:C); dexamethasone was also active. Furthermore, while progesterone and dexamethasone inhibited NO production under the same culture conditions, neither agent blocked the production of particles stimulated by the NO donors dipropylenetriamine NONOate {(z)-1-[N-(3-aminopropyl)-N-(3-ammoniopropyl)amino] diazen-1-ium-1,2-diolate} and (z)-1-[(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium-1,2-diolate. Studies using RU486 to assess the role of hormone receptors indicated that while this agent blocked the inhibition of particle and NO production by dexamethasone, it did not affect the inhibition by progesterone. Together, these results indicate that progesterone but not estradiol can inhibit particle release by stimulated macrophages and suggest a mechanism that may contribute to the immunomodulatory effects of this sex hormone.

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“…RA or systemic lupus erythematosus), and may act as ‘replacement' therapy (rather than ‘pharmacologic' therapy) in the presence of decreased endogenous cortisol availability due to the chronicity of the disease [32,33] (fig. 2).…”

Section: The Circadian Use Optimizes Gc Treatment Of Ra and Adrenal Imentioning

confidence: 99%

Circadian Use of Glucocorticoids in Rheumatoid Arthritis

Cutolo

Sulli

Pincus

2014

Neuroimmunomodulation

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A clear temporal relationship exists in rheumatoid arthritis (RA) patients between increased nocturnal levels of pro-inflammatory cytokines, such as TNF-α and interleukin (IL)-6, pro-inflammatory hormones (i.e. melatonin, prolactin) and insufficient night production of the anti-inflammatory cortisol (circadian rhythm). Under long-standing chronic stress of disease, insufficient cortisol is available to inhibit an ongoing nocturnal immune/inflammatory reaction. Clinical RA symptoms follow the same circadian rhythm with highest morning severity. Chronotherapy with nighttime glucocorticoid (GC) availability optimizes the treatment of RA patients with low-dose GCs through more efficient targeting of mediators of the immune/inflammatory reaction during the night to be available on arising. Circadian use of low-dose, long-term prednisone, by using night-release formulations (ingested at 10 to 11 p.m.) especially in early RA patients, appears characterized by a significantly superior efficacy on decreasing morning stiffness and IL-6 serum levels, compared to conventional daytime immediate-release prednisone. Shift from medium-dose, immediate-release prednisone (over 7.5-10 mg/day) to night-release formulations GC low-dose, long-term chronotherapy requires a gradual passage, since the hypothalamic-pituitary-adrenal axis of the treated RA patients, potentially altered by a negative feedback induced by the medium/high daily exogenous GC administration, needs time to re-synchronize control of endogenous GC production into a circadian and more physiological nocturnal hormone availability/optimized efficacy.

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Exogenous and endogenous glucocorticoids in rheumatic diseases

Cited by 88 publications

References 59 publications

Clearance of pathological antibodies using biomimetic nanoparticles

Clearance of pathological antibodies using biomimetic nanoparticles

Effects of Progesterone and Estradiol Sex Hormones on the Release of Microparticles by RAW 264.7 Macrophages Stimulated by Poly(I:C)

Circadian Use of Glucocorticoids in Rheumatoid Arthritis

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