The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Jul 2001
ReviewEffects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis in children.
In adults, morning plasma cortisol levels are twice that of late afternoon and evening values. In children, a delay in the time of onset in peak cortisol levels has been observed in those treated with inhaled corticosteroids. Consequently, the single morning cortisol level has a low sensitivity for detecting adrenal insufficiency in children. ⋯ No effects on the HPA axis were detected in either children or adults. It is unlikely that children are more sensitive to corticosteroids than are adults. There seems to be little point in performing routine monitoring of adrenal function in children who are treated with intranasal corticosteroid treatment.
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J. Allergy Clin. Immunol. · Apr 2001
ReviewRole of IL-9 in the pathophysiology of allergic diseases.
Considerable evidence from both human and animal studies indicates that CD4(+) cells are the predominant cell type involved in the regulation of airway inflammation through the expression of T(H)2-type cytokines. The effects of T(H)2-type cytokines, particularly IL-4 and IL-5, on inflammatory and structural cells in airways have been studied in great detail. ⋯ The development of transgenic mice overexpressing IL-9 has suggested a key role for this cytokine in the development of the asthmatic phenotype, including eosinophilic inflammation, bronchial hyperresponsiveness, elevated IgE levels, and increased mucus secretion. IL-9 has been shown to act on many cell types involved in asthma, including T cells, B cells, mast cells, eosinophils, neutrophils, and epithelial cells, and thus might be important in the pathophysiology of allergic asthma.
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In the past several years, extensive studies on the mechanisms underlying IL-4 and IL-13 signaling have enabled us to gain insight into how these cytokines regulate immune responses. Because both IL-4 and IL-13 use the IL-4Ralpha as a receptor component, these cytokines activate many common signaling pathways. Both of these cytokines use Janus kinases (JAKs) to initiate signaling and activate signal transducer and activator of transcription-6 (STAT6), which is a transcription factor required for many of their biologic functions. ⋯ In addition, IL-4 can activate a number of phosphatases including SH2-containing inositol phosphatase (SHIP), SHP-1, and SHP-2. Finally, B-cell lymphoma gene-6 (BCL-6) appears to regulate a subset of IL-4-induced genes. Thus the biologic responses induced by IL-4/IL-13 require a complex interaction of signaling pathways and regulators.
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Inhaled corticosteroids have now become established as first-line therapy for patients with persistent asthma. Corticosteroids are the only currently available asthma therapy that suppress inflammation in asthmatic airways, and they inhibit almost every aspect of the inflammatory process in asthma. Inhaled corticosteroids are effective in most patients with asthma, irrespective of age or asthma severity. ⋯ Inhaled corticosteroids are convenient to use and are the most cost-effective treatment currently available for long-term asthma control. A small proportion of patients are resistant to the antiinflammatory effects of corticosteroids. Future developments may include inhaled corticosteroids with even fewer systemic effects or more specific antiinflammatory drugs.
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J. Allergy Clin. Immunol. · Apr 1998
ReviewClinical relevance of inhaled corticosteroids and HPA axis suppression.
Although hypothalamic-pituitary-adrenal (HPA) axis suppression has traditionally been viewed as an adverse event after long-term administration of corticosteroids, this effect can also be used to compare the potency of different inhaled corticosteroids. However, various factors such as the dose, frequency of administration, treatment duration, study population (patients with asthma versus normal volunteers), and prior systemic steroid therapy influence adrenal suppression with inhaled corticosteroids. ⋯ Whereas low doses of inhaled corticosteroids are likely to cause minimal or no HPA axis suppression, long-term high-dose inhaled corticosteroid use may result in significant suppression by effectively replacing endogenous steroid production. The risk of acute adrenal insufficiency in patients taking low/medium-dose inhaled corticosteroids is minimal, but patients receiving long-term high-dose treatment may require supplementary systemic steroids during stress challenges, especially if they have previously received long-term systemic steroid treatment.