Mechanisms and resistance in glucocorticoid control of inflammation

Barnes, Peter J.

doi:10.1016/j.jsbmb.2010.02.018

Cited by 263 publications

(222 citation statements)

References 82 publications

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“…Recent insights into the molecular mechanisms and cellular resistance to glucocorticosteroids' control of inflammation in other autoimmune disease have been reviewed in detail elsewhere, e.g. [8,9]. Steroids can inhibit certain enzymes (such as calcium-dependent, mitogen-activated protein kinase/MAPK phosphorylation) essential for neuroprotection and hence hinder survival of neuronal cells during an inflammation [10].…”

Section: Chemistry and Mechanisms Of Actionmentioning

confidence: 99%

Steroids Impact on Myelin Repair, Neurogenesis and Visual Pathway in Multiple Sclerosis: Preclinical Perspectives

2017

j of exper clin neur

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Ab s t r a c tEven though steroids have drawn significant therapeutic interests for decades, data about their benefits for neural regeneration are missing as current observational studies unfold progressive abnormalities in cerebral gray matter and cerebellum compartments, apart from demyelination lesions in white matter of the central nervous system (CNS) in multiple sclerosis (MS). This medical-scientific appraisal is based on a series of structured questions in part addressed in our investigative clinical review on the benefits and risks of glucocorticosteroids (GC), which highlights that steroids can intensify the disease progression, aside from other global side effects recognized in MS and associated optic neuritis (MS-ON). Corticosteroids treatments, whilst temporally and selectively suppress immune reactions, can interfere with the clearance of myelin debris and inhibit proliferation-migration of the myelinating cells, affecting the axonal repair and CNS functions. This review compiles and summarizes datasets extracted largely from complementary laboratory studies published in Medline, It discusses related pharmacologic and disease mechanisms and relevancies of the distinct MS disease models in rodents, with emphasis on the strengths and weaknesses of the associations of GCs use, glucocorticoid receptors sensitivity, and clinical outcomes. Based on these assessments, we conclude that steroids can suppress inflammation to the determent of neuronal remodeling in a mutually exclusive manner. Excess steroids can contribute to neuronal loss and retinal damage in optic pathology, and thus may expand cerebral atrophy and disease burden in multiple sclerosis.

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Section: Chemistry and Mechanisms Of Actionmentioning

confidence: 99%

Steroids Impact on Myelin Repair, Neurogenesis and Visual Pathway in Multiple Sclerosis: Preclinical Perspectives

2017

j of exper clin neur

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“…[19][20][21][22] El comportamiento de la enfermedad durante los 6 primeros meses luego de haber completado el tratamiento inicial predice el pronóstico a largo plazo. Datos provenientes del ISKDC demostraron que de 148 niños que permanecieron en remisión durante los 6 meses luego del episodio inicial, el 76% nunca recayó o lo hicieron en forma infrecuente.…”

Section: Corticoidesunclassified

Consenso de tratamiento del síndrome nefrótico en la infancia

2014

Arch Argent Pediat

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“…Although recent studies yielded a number of possible mechanisms to explain this insensitivity, the central hypothesis implies the increase in oxidant burden within the lungs, resulting in reduction in the activity of histone deacetylase (HDAC)-2. Accordingly, increasing the HDAC2-activity by PDE-inhibitors, phosphoinositide 3 kinase-delta inhibitors and macrolides could result in a reversal of corticosteroid resistance [53].…”

Section: Roflumilast: Pharmacokinetics Clinical Efficacy From Phase mentioning

confidence: 99%

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

Diamant

Spina

2011

Pulmonary Pharmacology & Therapeutics

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SummaryRoflumilast is a selective once daily, oral phosphodiesterase-4 inhibitor that has recently been registered in all European Union countries as novel targeted therapy for COPD, while FDA approval for the USA market is expected in 2011. In several phase III trials in patients with moderate to (very) severe COPD and in patients with symptoms of chronic bronchitis and recurrent exacerbations, roflumilast showed sustained clinical efficacy by improving lung function and by reducing exacerbation rates. These beneficial effects have also been demonstrated when added to long-acting bronchodilators (both LABA and LAMA), underscoring the anti-inflammatory activity of roflumilast in COPD. Pooled data analysis showed overall mild to moderate, mostly self-limiting adverse events, mainly consisting of nausea, diarrhea and weight loss. In this review we discuss the results of the 4 registration studies showing promising effects of roflumilast in COPD and provide an overview of the topics that still need to be addressed. keywords: PDE4-inhibitor, roflumilast, clinical trials, chronic obstructive airways disease 3

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Mechanisms and resistance in glucocorticoid control of inflammation

Cited by 263 publications

References 82 publications

Steroids Impact on Myelin Repair, Neurogenesis and Visual Pathway in Multiple Sclerosis: Preclinical Perspectives

Steroids Impact on Myelin Repair, Neurogenesis and Visual Pathway in Multiple Sclerosis: Preclinical Perspectives

Consenso de tratamiento del síndrome nefrótico en la infancia

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

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