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Two well-established antiparasitic drugs, niclosamide and ivermectin, are intensively discussed for the treatment of viral inflammatory airway infections. Here, we examined these repurposed drugs with respect to their anti-inflammatory effects in airways <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Niclosamide reduced mucus content, eosinophilic infiltration and cell death in asthmatic mouse lungs <jats:italic>in vivo<\/jats:italic> and inhibited release of interleukins in the two differentiated airway epithelial cell lines CFBE and BCi-NS1.1 <jats:italic>in vitro<\/jats:italic>. Cytokine release was also inhibited by the knockdown of the Ca<jats:sup>2+<\/jats:sup>-activated Cl<jats:sup>\u2212<\/jats:sup> channel anoctamin 1 (ANO1, TMEM16A) and the phospholipid scramblase anoctamin 6 (ANO6, TMEM16F), which have previously been shown to affect intracellular Ca<jats:sup>2+<\/jats:sup> levels near the plasma membrane and to facilitate exocytosis. At concentrations around 200\u00a0nM, niclosamide inhibited inflammation, lowered intracellular Ca<jats:sup>2+<\/jats:sup>, acidified cytosolic pH and blocked activation of ANO1 and ANO6. It is suggested that niclosamide brings about its anti-inflammatory effects at least in part by inhibiting ANO1 and ANO6, and by lowering intracellular Ca<jats:sup>2+<\/jats:sup> levels. In contrast to niclosamide, 1\u00a0\u00b5M ivermectin did not exert any of the effects described for niclosamide. The present data suggest niclosamide as an effective anti-inflammatory treatment in CF, asthma, and COVID-19, in addition to its previously reported antiviral effects. It has an advantageous concentration\u2013response relationship and is known to be well tolerated.<\/jats:p>","DOI":"10.1007\/s00424-023-02878-w","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T07:02:00Z","timestamp":1700290920000},"page":"211-227","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Niclosamide, but not ivermectin, inhibits anoctamin 1 and 6 and attenuates inflammation of the respiratory tract"],"prefix":"10.1007","volume":"476","author":[{"given":"Jiraporn","family":"Ousingsawat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Centeio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kunzelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"2878_CR1","doi-asserted-by":"publisher","first-page":"5833","DOI":"10.1002\/jmv.27122","volume":"93","author":"S Abd-Elsalam","year":"2021","unstructured":"Abd-Elsalam S, Noor RA, Badawi R, Khalaf M, Esmail ES, Soliman S, Abd El Ghafar MS, Elbahnasawy M, Moustafa EF, Hassany SM, Medhat MA, Ramadan HK, Eldeen MAS, Alboraie M, Cordie A, Esmat G (2021) Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: a randomized controlled study. 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