The effects of prednisolone on the cutaneous tuberculin response in patients with corticosteroid-resistant bronchial asthma

Lane, Stephen; Atkinson, Beryl A.; Poston, Robin N.; Lee, Tak H.

doi:10.1016/s0091-6749(96)70317-2

Cited by 19 publications

(8 citation statements)

References 33 publications

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“…In patients with GCR asthma a reduced blanching response to topical glucocorticoids applied to the skin further indicates that there is a generalized abnormality that is unlikely to be secondary to local cytokine production [146]. In patients with GCS asthma there was suppression of the cutaneous tuberculin response after treatment for 2 weeks with oral prednisolone associated with reduced numbers of macrophages, eosinophils and activated T-lymphocytes, but this was not observed in GCR patients [147].…”

Section: Mechanisms Of Glucocorticoid Resistancementioning

confidence: 99%

Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms

1998

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1. Glucocorticoids are widely used for the suppression of inflammation in chronic inflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease and autoimmune diseases, all of which are associated with increased expression of inflammatory genes. The molecular mechanisms involved in this anti-inflammatory action of glucocorticoids is discussed, particularly in asthma, which accounts for the highest clinical use of these agents. 2. Glucocorticoids bind to glucocorticoid receptors in the cytoplasm which then dimerize and translocate to the nucleus, where they bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, resulting in increased transcription. Glucocorticoids may increase the transcription of genes coding for anti-inflammatory proteins, including lipocortin-1, interleukin-10, interleukin-1 receptor antagonist and neutral endopeptidase, but this is unlikely to account for all of the widespread anti-inflammatory actions of glucocorticoids. 3. The most striking effect of glucocorticoids is to inhibit the expression of multiple inflammatory genes (cytokines, enzymes, receptors and adhesion molecules). This cannot be due to a direct interaction between glucocorticoid receptors and GRE, as these binding sites are absent from the promoter regions of most inflammatory genes. It is more likely to be due to a direct inhibitory interaction between activated glucocorticoid receptors and activated transcription factors, such as nuclear factor-kappa B and activator protein-1, which regulate the inflammatory gene expression. 4. It is increasingly recognized that glucocorticoids change the chromatin structure. Glucocorticoid receptors also interact with CREB-binding protein (CBP), which acts as a co-activator of transcription, binding several other transcription factors that compete for binding sites on this molecule. Increased transcription is associated with uncoiling of DNA wound around histone and this is secondary to acetylation of the histone residues by the enzymic action of CBP. Glucocorticoids may lead to deacetylation of histone, resulting in tighter coiling of DNA and reduced access of transcription factors to their binding sites, thereby suppressing gene expression. 5. Rarely patients with chronic inflammatory diseases fail to respond to glucocorticoids, although endocrine function of steroids is preserved. This may be due to excessive formation of activator protein-1 at the inflammatory site, which consumes activated glucocorticoid receptors so that they are not available for suppressing inflammatory genes. 6. This new understanding of glucocorticoid mechanisms may lead to the development of novel steroids with less risk of side effects (which are due to the endocrine and metabolic actions of steroids). 'Dissociated' steroids which are more active in transrepression (interaction with transcription factors) than transactivation (GRE binding) have now been developed. Some of the transcription factors that are inhibited by glucocorticoid, such as nuclear factor-k...

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Section: Mechanisms Of Glucocorticoid Resistancementioning

confidence: 99%

Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms

1998

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“…A recent meta‐analysis stated that the overall sensitivity of the TST for active tuberculosis is 77%; 191 however, the sensitivity of the test can be dramatically impaired, for example, in infants and toddlers 192 as well as in elderly persons, 193 in individuals with congenital or acquired immunodeficiencies (e.g. those with HIV infection 194–196 ), patients being treated with corticosteroids 197 or other immunosuppressive drugs, 198 patients with chronic renal failure, 199,200 malnutrition, 201,202 cancer 203 or overt forms of tuberculosis 204,205 . The specificity of the TST is dependent on the BCG vaccination status 206 and the immune status of the individual who is tested 191 .…”

Section: Immunological Diagnosismentioning

confidence: 99%

Advances in the diagnosis of tuberculosis

2010

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Tuberculosis ranges among the leading causes of morbidity and mortality worldwide. A diagnostic approach to a patient with possible tuberculosis includes a detailed medical history and clinical examination as well as radiological, microbiological, immunological, molecular-biological and histological investigations, where available. Recently, important advances have been achieved in these fields that have led to substantial improvements in the accuracy and the timing of the diagnosis of tuberculosis. Novel methods allow for a better identification of latently infected individuals who are at risk of developing active tuberculosis, they also offer the possibility for a rapid diagnosis of active tuberculosis in patients with negative sputum smears for acid-fast bacilli and enable prompt identification of drug-resistant strains of Mycobacterium tuberculosis directly from respiratory specimen with a high accuracy. In addition, promising methods that will further optimize the diagnosis of tuberculosis are under development. In the future, therapeutic interventions based on the results of novel diagnostic procedures can be made earlier leading to improvements in patient care.

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“…We have demonstrated decreased suppression by pred nisolone of macrophage, T lymphocyte and eosinophil in filtration into the cutaneous tuberculin response in CR as opposed to CS subjects, which was not associated with dif ferences in vascular adhesion molecule expression [14]. Leung et al [15] have demonstrated reduced suppression of eosinophil and T cell infiltration into the broncho-alveolar lavage fluid after prednisolone therapy in CR subjects.…”

Section: In Vivo Cellular Defects In Cr a Sthm Amentioning

confidence: 53%

Mechanisms of Corticosteroid Resistance in Asthmatic Patients

Lane

Lee²

1997

Int Arch Allergy Immunol

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Corticosteroid-resistant (CR) asthma is associated with disease chronicity, a more frequent family history of asthma and impaired in vitro and in vivo responsiveness of peripheral blood mononuclear cells to the suppressive effects of glucocorticoids. CR asthma is associated with normal suppression of the hypothalamic-pituitary-adrenal axis and of biochemical indices of bone turnover by dexamethasone, indicating that the phenomenon of glucocorticoid resistance is specific to inflammatory leukocytes and that these patients are equally at risk of developing ‘cushingoid’ side effects. We have been unable to detect altered bioavailability of administered glucocorticoid, impaired ligand binding or nuclear translocation of the activated glucocorticoid receptor (GR) complex or structural abnormalities of the GR cDNA in our population of CR asthmatics. We have recently demonstrated that CR asthma is associated with decreased GR and increased AP-1 (Fos; Jun) DNA binding in peripheral blood mononuclear cells as compared to corticosteroid-sensitive asthma. These results highlight the central role of the AP-1/GR interactions in glucocorticoid action in CR asthma.

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The effects of prednisolone on the cutaneous tuberculin response in patients with corticosteroid-resistant bronchial asthma

Cited by 19 publications

References 33 publications

Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms

Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms

Advances in the diagnosis of tuberculosis

Mechanisms of Corticosteroid Resistance in Asthmatic Patients

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