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Anti-inflammatory effects of ivermectin in mouse model of allergic asthma

Yan et al., Inflammation Research, doi:10.1007/s00011-011-0307-8
Jan 2011  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 111 treatments. c19ivm.org
Mouse study showing ivermectin significantly reduced airway inflammation, Th2 cytokine production, mucus hypersecretion, and airway hyperresponsiveness in a mouse model of allergic asthma. Ivermectin lessened lung inflammation by decreasing inflammatory cell infiltration, mucus production, and IgE levels. The anti-inflammatory effects were similar to the steroid dexamethasone. Since uncontrolled inflammation and cytokine storm are major issues in severe COVID-19, these anti-inflammatory and immunomodulatory effects suggest ivermectin could potentially help prevent damaging inflammatory responses in the lungs that lead to respiratory failure.
70 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N768, Dengue34,69,70, HIV-170, Simian virus 4071, Zika34,72,73, West Nile73, Yellow Fever74,75, Japanese encephalitis74, Chikungunya75, Semliki Forest virus75, Human papillomavirus54, Epstein-Barr54, BK Polyomavirus76, and Sindbis virus75.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins68,70,71,77, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing35, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination38,78, shows dose-dependent inhibition of wildtype and omicron variants33, exhibits dose-dependent inhibition of lung injury58,63, may inhibit SARS-CoV-2 via IMPase inhibition34, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation7, inhibits SARS-CoV-2 3CLpro51, may inhibit SARS-CoV-2 RdRp activity26, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages57, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation79, may interfere with SARS-CoV-2's immune evasion via ORF8 binding2, may inhibit SARS-CoV-2 by disrupting CD147 interaction80-83, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1956,84, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage6, may minimize SARS-CoV-2 induced cardiac damage37,45, increases Bifidobacteria which play a key role in the immune system85, has immunomodulatory48 and anti-inflammatory67,86 properties, and has an extensive and very positive safety profile87.
Yan et al., 29 Jan 2011, peer-reviewed, 8 authors. Contact: xumingdeng@jluhp.edu.cn.
This PaperIvermectinAll
Anti-inflammatory effects of ivermectin in mouse model of allergic asthma
Shuhan Yan, Xinxin Ci, Na Chen, Chi Chen, Xiangchao Li, Xiao Chu, Jianhua Li, Xuming Deng
Inflammation Research, doi:10.1007/s00011-011-0307-8
Background and objective Asthma is an inflammatory disease of the lungs that is characterised by increased inflammatory cell infiltration into the airways and poor respiratory function. Ivermectin is a semi-synthetic derivative of a family of macrocyclic lactones that shows broad-spectrum anti-parasitic activity. This drug has been shown to possess anti-inflammatory activity, but whether it can be used in asthma treatment has not yet been investigated. In this study, we aimed to investigate the inhibitory effects of ivermectin on allergic asthma symptoms in mice. Methods and results We used a mouse asthma model, in which allergic airway inflammation and airway remodelling were induced by ovalbumin (OVA) sensitisation and challenge. Ivermectin or PBS treatment was administered 1 h before OVA challenge. Ivermectin at 2 mg/kg significantly diminished recruitment of immune cells, production of cytokines in the bronchoalveolar lavage fluids and secretion of OVA-specific IgE and IgG1 in the serum. Histological studies indicated that ivermectin suppressed mucus hypersecretion by goblet cells in the airway. Conclusions This is the first study to demonstrate that ivermectin is an effective suppressor of inflammation and may be efficacious in the treatment of non-infectious airway inflammatory diseases such as allergic asthma.
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' '1998;273:3285–90.', 'journal-title': 'J Biol Chem'}], 'container-title': 'Inflammation Research', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://link.springer.com/content/pdf/10.1007/s00011-011-0307-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'http://link.springer.com/article/10.1007/s00011-011-0307-8/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'http://link.springer.com/content/pdf/10.1007/s00011-011-0307-8', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2019, 6, 8]], 'date-time': '2019-06-08T06:01:31Z', 'timestamp': 1559973691000}, 'score': 1, 'resource': {'primary': {'URL': 'http://link.springer.com/10.1007/s00011-011-0307-8'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2011, 1, 29]]}, 'references-count': 37, 'journal-issue': {'issue': '6', 'published-print': {'date-parts': [[2011, 6]]}}, 'alternative-id': ['307'], 'URL': 'http://dx.doi.org/10.1007/s00011-011-0307-8', 'relation': {}, 'ISSN': ['1023-3830', '1420-908X'], 'subject': ['Pharmacology', 'Immunology'], 'container-title-short': 'Inflamm. Res.', 'published': {'date-parts': [[2011, 1, 29]]}}
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