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All Studies   Meta Analysis    Recent:   

Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice

Zhang et al., Inflammation Research, doi:10.1007/s00011-008-8007-8
Nov 2008  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 102 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments. c19ivm.org
Analysis of ivermectin's effects in mouse models of lethal endotoxemia, which mimics key pathological features seen in severe and critical COVID-19 cases.
Pretreatment with ivermectin significantly improved survival rates in mice given a lethal dose of LPS. Ivermectin also substantially reduced inflammatory cytokine levels (TNF-α, IL-1β, IL-6) in the mouse model and in LPS-stimulated macrophages. The anti-inflammatory effects were associated with inhibition of NF-kB activation, a key inflammatory pathway. Overall, the results show promising anti-inflammatory and protective effects in models of severe infection/inflammation.
The LPS mouse model reflects several key pathological features of severe and critical COVID-19, including:
- excessive inflammation - LPS administration in mice and severe COVID-19 can lead to an uncontrolled inflammatory response, involving a dramatic increase in inflammatory cytokines like TNF-α, IL-1β, and IL-6. This cytokine storm is thought to underlie much of the organ damage in severe COVID-19.
- tissue damage/organ failure - the excessive inflammation can lead to damage of lung tissue as well as failure of other organs like the kidneys in both LPS models and COVID-19.
- activation of the NF-kB pathway - the inflammatory response in both cases involves activation of the NF-kB pathway in immune cells like macrophages. NF-kB drives transcription of inflammatory cytokines.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Jitobaom, Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Jitobaom, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), inhibits SARS-CoV-2 3CLpro Mody, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 via IMPase inhibition Jitobaom, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacteria which play a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Zhang et al., 13 Nov 2008, peer-reviewed, 10 authors. Contact: xumingdeng@jluhp.edu.cn, jcui@wyeth.com.
This PaperIvermectinAll
Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice
X Zhang, Y Song, X Ci, N An, Y Ju, H Li, X Wang, C Han, J Cui, X Deng
Inflammation Research, doi:10.1007/s00011-008-8007-8
Objective and Design: To investigate whether ivermectin, a semi-synthetic derivative of a family of macrocyclic lactones could inhibit lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. Materials and Methods: C57BL/6 mice were administered ivermectin (or saline) orally and challenged intraperitoneally with LPS at a lethal dose of 32 mg/kg. RAW 264.7 murine macrophages were stimulated with LPS at 1 µg/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in serum from mice and supernatants from cells were measured by ELISA. Nuclear factor-kB (NF-kB) translocation with subunit p65 was evaluated by immunocytochemical analysis. Results: Ivermectin improved mouse survival rate induced by a lethal dose of LPS. In addition, ivermectin significantly decreased the production of TNF-a, IL-1ß and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB translocation induced by LPS. Conclusions: The results indicate that ivermectin may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB pathway and improve LPS-induced survival in mice. This finding might provide a new strategy for the treatment of endotoxemia and associated inflammation.
References
Adamis, Laoutaris, Sabracos, Koussoulas, Mouktaroudi, Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa, Antimicrob Agents Chemother
Ahmed, Anuntiyo, Malemud, Haqqi, Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: A review, Evid Based Complement Alternat Med
Angus, Linde-Zwirble, Lidicker, Clermont, Carcillo et al., Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care, Crit. Care Med
Annane, Aegerter, Jars-Guincestre, Guidet, Current epidemiology of septic shock: the CUB-Rea Network, Am J Respir Crit Care Med
Cannon, Tompkins, Gelfand, Michie, Stanford et al., Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever, J Infect Dis
Caumes, Danis, New indications of ivermectin, Rev Med Interne
Cohen, The immunopathogenesis of sepsis, Nature
Delgado, Mcmanus, Chambers, Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P, Neuropeptides
Develoux, Ivermectin, None, Ann Dermatol Venereol
Didier, Loor, Decreased biotolerability for ivermectin and cyclosporin A in mice exposed to potent P-glycoprotein inhibitors, Int J Cancer
Ej, Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators, Int J Antimicrob Agents
Flohé, Brigelius-Flohé, Saliou, Traber, Packer, Redox regulation of NF-kappa B activation, Free Radic Biol Med
Geary, Ivermectin 20 years on: maturation of a wonder drug, Trends Parasitol
Glauser, The inflammatory cytokines. New developments in the pathophysiology and treatment of septic shock, Drugs
Guha, Mackman, LPS induction of gene expression in human monocytes, Cell Signal
Hajime, Kazuhito, Yoshiyuki, So, Tadashi, Suppressive activity of macrolide antobiotics on nitric oxide production by lipopolysaccharide stimulation in mice, Mediators of inflamm
Ianaro, Ialenti, Maffia, Sautebin, Rombola et al., Anti-inflammatory activity of macrolide antibiotics, J Pharmacol Exp Ther
Ivetic, Tkalcevic, Bosnjak, Hrvacic, Bosnar et al., Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice, Eur J Pharmacol
Leiva, Ruiz-Bravo, Moreno, Jimenez-Valera, The antiinflammatory activity of telithromycin in a mouse model of septic shock, Int J Antimicrob Agents
Mannel, Echtenacher, TNF in the inflammatory response, Chem Immunol
Marks, Marks, Luce, Montgomery, Turner et al., Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration, Am Rev Respir Dis
Mayeux, Pathobiology of lipopolysaccharide, J Toxicol Environ Health
Miller, Ernst, Bader, LPS, TLR4 and infectious disease diversity, Nat Rev Microbiol
Miyake, Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2, Trends Microbiol
Parillo, Pathogenetic mechanisms of septic shock, N Engl J Med
Parrillo, Parker, Natanson, Suffredini, Danner et al., Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction and therapy, Ann Intern Med
Richard-Lenoble, Chandenier, Gaxotte, Ivermectin and filariasis, Fundam Clin Pharmacol
Sajid, Iqbal, Muhammad, Iqbal, Immunomodulatory effect of various anti-parasitics: a review, Parasitology
Silva, Mde, Sogayar, Mohovic, Silva et al., Brazilian sepsis epidemiological study, Crit Care
Stankiewicz, Cabaj, Moore, Millar, Ng Chie, Influence of ivermectin on cellular and humoral immune responses of lambs, Vet Immunol Immunopathol
Tian, Brasier, Identification of a nuclear factor kappa B-dependent gene network, Recent Prog Horm Res
Viktorov, Ivermectin inhibits activation of Kupffer cells induced by lipopolysaccharide toxin, Antibiot Khimioter
Viktorov, Yurkiv, Effect of ivermectin on function of liver macrophages, Bull Exp Biol Med
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