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Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献![点击此处可从《Pediatric dermatology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rates of mental illness have increased dramatically over the past 15 years in the United States [Products—Data Briefs—Number 283—August 2017. Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/products/databriefs/db283.htm. Published August 15, 2017]. Additionally, life expectancy has fallen over the past several years due to increases in death from suicide, opioid overdose, and alcoholic liver cirrhosis as reported by Case and Deaton [Deaths of despair and the future of capitalism. Princeton University Press, 2020]. Over the last decade some have questioned whether these changes are due to neoliberal capitalist policies and ideologies. Neoliberal capitalism incorporates theories of eliminating all restrictions on the market and decreasing government assistance programs as reported by Harvey [A brief history of neoliberalism, Oxford University Press, 2005]. Since then these policies have led to income inequality, disempowerment of workers, outsourcing of manufacturing jobs, inadequate social services, mass incarceration and an expensive and ineffective healthcare system as reported by Case and Deaton [Deaths of despair and the future of capitalism. Princeton University Press, 2020] and Nkansah-Amankra et al. [International Journal of Health Services 43(2):217-240, 2013]. Studies have shown that the consequences of these policies and ideologies likely have a role in increasing rates of mental illness. This paper will discuss how these factors increase mental distress and postulate ways that mental health professionals can advocate for change.
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