{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T21:21:08Z","timestamp":1783372868018,"version":"3.54.6"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Interleukin (IL)\u201010 is a key anti\u2010inflammatory cytokine that may be reduced in asthma but is enhanced by corticosteroids, especially when combined with a statin, although the mechanisms of these effects are uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To study the role of autophagy in macrophages in promoting inflammation in asthma through reducing IL\u201010 secretion and how corticosteroids and statins may reverse this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a randomised double\u2010blind placebo\u2010controlled study in moderate to severe asthmatic patients (n\u00a0=\u00a044) to investigate the effect of an inhaled corticosteroid (budesonide 400\u00a0\u03bcg\/day) and the combination of budesonide with an oral statin (simvastatin 10\u00a0mg\/day) given for 8\u00a0weeks on autophagy protein expression in sputum cells by using immunocytochemistry and measurement of IL\u201010 release. In <jats:italic>in vitro<\/jats:italic> experiments, we studied cross\u2010regulation between autophagy and IL\u201010 release by measuring the expression of autophagy proteins in M2\u2010like macrophages and the effects of budesonide and simvastatin on these mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In asthmatic patients, inhaled budesonide inhibited airway macrophage autophagy (beclin\u20101, LC3) as well as autophagic flux (p62), which was enhanced by simvastatin and was correlated with increased sputum IL\u201010 and reduced IL\u20104 concentrations. In macrophages <jats:italic>in vitro<\/jats:italic>, budesonide and simvastatin inhibited rapamycin\u2010induced autophagy as well as autophagic flux, with reduced expression of beclin\u20101 and LC3, but enhanced the accumulation of p62 and increased expression of IL\u201010, which itself further inhibited autophagy in macrophages. With siRNA\u2010mediated silencing, LC3\u2010deficient macrophages also showed a maximal induction of IL\u201010 transcription. Neutralisation of IL\u201010 with recombinant specific blocking antibody and silencing IL\u201010 transcription reversed the inhibitory effects of budesonide and simvastatin on macrophage autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and clinical relevance<\/jats:title><jats:p>Inhibition by corticosteroids and a statin of macrophage autophagy enhances IL\u201010 production, resulting in the control of asthmatic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13825","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T03:25:19Z","timestamp":1610681119000},"page":"1553-1565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Role of autophagy in regulating interleukin\u201010 and the responses to corticosteroids and statins in 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