Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulation of eosinophils in the bronchial tissue occurs in a variety of inflammatory disorders of the human airway. We asked whether airway epithelial cells released factors that could influence eosinophil survival and thus contribute to accumulation of these cells in the tissues. Using conditioned medium (CM) generated from cultured human bronchial epithelial cells (HBEC), we examined the in vitro survival of eosinophils isolated from human peripheral blood. When cultured in control medium, more than 90% of the eosinophils were dead by day 4. In contrast, culture in HBEC-CM resulted in dose-dependent survival at day 6 of 69 +/- 9.4%, 40.5 +/- 5.9%, and 25 +/- 2% viability with 2, 0.5, and 0.1% HBEC-CM, respectively (n = 4). Granulocyte/macrophage colony-stimulating factor (GM-CSF) was detected in the HBEC-CM by enzyme-linked immunosorbent assay at levels of 22 to 48 pg/ml. Furthermore, preincubation of the HBEC-CM with a neutralizing monoclonal antibody to human GM-CSF completely inhibited this increased survival of eosinophils. Because corticosteroids are potent eosinopenic agents, we also examined the effects of the synthetic steroid budesonide on this system. Budesonide inhibited both spontaneous and interleukin-1 (IL-1)-induced GM-CSF production by cultured HBEC. In addition, preincubation of eosinophils with budesonide caused marked abrogation of the survival induced subsequently with either HBEC-CM or recombinant human GM-CSF. In summary, HBEC can support eosinophil survival via the elaboration of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation. Steroids may modulate this process both by inhibiting cytokine production from HBEC and by a direct effect on eosinophils, preventing their response to cytokines.
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PMID:Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids. 205 93

Chronic obstructive pulmonary disease (COPD) is a progressive disease with alveolar destruction (emphysema) and bronchiolar fibrosis (obstructive bronchitis) in variable proportions. Reducing disease progression, as assessed by forced expiratory volume in I second (FEV1) decline, health-related quality of life, exacerbation rate and mortality, is a more realistic outcome than physiological improvement. This paper reviews all the published studies of at least 100 patients followed for at least 2 years. Studies have included patients with mild COPD (Copenhagen City Lung Study) to advanced symptomatic disease [Inhaled Steroids in Obstructive Lung Disease (ISOLDE)], with 2 studies of those with relatively early symptoms [European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) and Lung Health-21. Exacerbation frequency, and probably severity, are reduced by high dose inhaled corticosteroids. Exacerbations are only frequent in more advanced disease, limiting the use of this outcome in EUROSCOP and Lung Health-2. Exacerbations are associated with reduced health-related quality of life. ISOLDE clearly showed a reduced rate in decline of the disease-specific St George's Respiratory Questionnaire with fluticasone propionate, partly related to the reduced exacerbations. The symptom component of the score showed the greatest difference between placebo and fluticasone propionate. None of the larger studies were able to reproduce the statistically significant reduction in the rate of decline in FEV1 suggested by the smaller, earlier studies. This might at least in part be as a result of the statistical modelling used which cannot adequately compensate for those with more rapidly progressive disease dropping out earlier. The equivalent doses of inhaled corticosteroids differed approximately fivefold between the major studies. The more positive results were obtained with higher doses. Oropharyngeal adverse effects were similar to those seen in patients with asthma; bruising was increased in one study with budesonide, otherwise adverse effects were similar to placebo. Bone loss was specifically studied in subgroups of patients in EUROSCOP and Lung Health-2. Budesonide 800 microg/day was associated with less bone loss than placebo, whereas triamcinolone 1200 microg/day was associated with excess bone loss. High dose inhaled corticosteroids have a favourable risk/benefit ratio in patients with advanced disease, particularly those with frequent exacerbations, and no benefit for those with very mild disease. It is not possible from the data to make firm recommendations for the important intermediate group where delaying progression is likely to lead to greatest benefit. I believe high dose inhaled steroids are warranted for those with intermediate severity COPD, who have frequent exacerbations or significant COPD-related symptoms.
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PMID:Should inhaled corticosteroids be used in the long term treatment of chronic obstructive pulmonary disease? 1157 91

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.
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PMID:[Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH]. 1677 19

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and the most common cause of end-stage renal disease in young adults. However, there are still no specific therapies capable of targeting key pathways involved in disease pathogenesis. Recently, many large randomized controlled trials have been reported, such as Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy, Targeted-release Budesonide Versus Placebo in Patients with IgA Nephropathy and Therapeutic Evaluation of Steroids in IgA Nephropathy Global, which are considered to update the 2012 Kidney Disease: Improving Global Outcomes Guideline. More importantly, with a deeper understanding of the roles of mucosal immunity, B-cell activation and complement activation in IgAN, the studies of targeting pathogenic pathways are ongoing. In this review, by systemically searching the clinical trials in IgAN on ClinicalTrials.gov (https://clinicaltrials.gov/), we update the evidence for corticosteroids/immunosuppressive therapy in IgAN and explore the promising targeting pathogenic pathway therapeutic options. With better understanding of pathogenesis of IgAN, emerging therapies will soon become a reality in future.
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PMID:Update on treatment of immunoglobulin A nephropathy. 3029 61