Skip to main content
Erschienen in: Inflammation Research 6/2011

01.06.2011 | Original Research Paper

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

verfasst von: Shuhan Yan, Xinxin Ci, Na Chen, Chi Chen, Xiangchao Li, Xiao Chu, Jianhua Li, Xuming Deng

Erschienen in: Inflammation Research | Ausgabe 6/2011

Einloggen, um Zugang zu erhalten

Abstract

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.
Literatur
1.
Zurück zum Zitat Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z. New insights into the pathogenesis of asthma. J Clin Invest. 2003;111:291–7.PubMed Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z. New insights into the pathogenesis of asthma. J Clin Invest. 2003;111:291–7.PubMed
2.
Zurück zum Zitat Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol. 1999;17:255–81.PubMedCrossRef Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol. 1999;17:255–81.PubMedCrossRef
3.
Zurück zum Zitat Anderson GP, Coyle AJ. Th2 and ‘Th2-like’ cells in allergy and asthma: pharmacological perspectives. Trends Pharmacol Sci. 1994;15:324–32.PubMedCrossRef Anderson GP, Coyle AJ. Th2 and ‘Th2-like’ cells in allergy and asthma: pharmacological perspectives. Trends Pharmacol Sci. 1994;15:324–32.PubMedCrossRef
4.
5.
Zurück zum Zitat Bryskier A, Agouridas C, Chantot JF. New medical targets for macrolides. Exp Opin Invest Drugs. 1994;3:405–10.CrossRef Bryskier A, Agouridas C, Chantot JF. New medical targets for macrolides. Exp Opin Invest Drugs. 1994;3:405–10.CrossRef
6.
Zurück zum Zitat Tarayre JP, Aliaga M, Barbara M, Villanova G, Ballester R, Tisne-Versailles J, et al. Cutaneously applied erythromycin base reduces various types of inflammatory reactions in mouse ear. Int J Tiss Reac. 1987;4:77–85. Tarayre JP, Aliaga M, Barbara M, Villanova G, Ballester R, Tisne-Versailles J, et al. Cutaneously applied erythromycin base reduces various types of inflammatory reactions in mouse ear. Int J Tiss Reac. 1987;4:77–85.
7.
Zurück zum Zitat Mikasa K, Kita E, Sawaki M, Kunimatsu M, Hamada K, Konishi M, et al. The anti-inflammatory effect of erythromycin in zymosan-induced peritonitis of mice. J Antimicrob Chemother. 1992;30:339–48.PubMedCrossRef Mikasa K, Kita E, Sawaki M, Kunimatsu M, Hamada K, Konishi M, et al. The anti-inflammatory effect of erythromycin in zymosan-induced peritonitis of mice. J Antimicrob Chemother. 1992;30:339–48.PubMedCrossRef
8.
Zurück zum Zitat Agen C, Danesi R, Blandizzi C, Costa M, Stacchini B, Favini P, et al. Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role. Agents Actions. 1993;38:85–90.PubMedCrossRef Agen C, Danesi R, Blandizzi C, Costa M, Stacchini B, Favini P, et al. Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role. Agents Actions. 1993;38:85–90.PubMedCrossRef
9.
Zurück zum Zitat Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents. 2008;31:12–20.PubMedCrossRef Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents. 2008;31:12–20.PubMedCrossRef
10.
Zurück zum Zitat Hrvačić B, Bošnjak B, Bosnar M, Ferenčić Ž, Glojnarić I, Eraković Haber V. Clarithromycin suppresses airway hyperresponsiveness and inflammation in mouse models of asthma. Eur J Pharmacol. 2009;15:236–43. Hrvačić B, Bošnjak B, Bosnar M, Ferenčić Ž, Glojnarić I, Eraković Haber V. Clarithromycin suppresses airway hyperresponsiveness and inflammation in mouse models of asthma. Eur J Pharmacol. 2009;15:236–43.
11.
Zurück zum Zitat Beigelman A, Gunsten S, Mikols CL, Vidavsky I, Cannon CL, Brody SL, et al. Azithromycin attenuates airway inflammation in a noninfectious mouse model of allergic asthma. Chest. 2009;136(2):498–506.PubMedCrossRef Beigelman A, Gunsten S, Mikols CL, Vidavsky I, Cannon CL, Brody SL, et al. Azithromycin attenuates airway inflammation in a noninfectious mouse model of allergic asthma. Chest. 2009;136(2):498–506.PubMedCrossRef
12.
13.
Zurück zum Zitat Stankiewicz M, Cabaj W, Jonas WE, Moore LG, Millar K, Ng Chie W. Influence of ivermectin on cellular and humoral immune responses of lambs. Vet Immunol Immunopathol. 1995;44:347–58.PubMedCrossRef Stankiewicz M, Cabaj W, Jonas WE, Moore LG, Millar K, Ng Chie W. Influence of ivermectin on cellular and humoral immune responses of lambs. Vet Immunol Immunopathol. 1995;44:347–58.PubMedCrossRef
14.
Zurück zum Zitat Zhang X, Song Y, Xiong H, Ci X, Li H, Yu L, et al. Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages. Int J Immunopharmacol. 2009;9:354–9.CrossRef Zhang X, Song Y, Xiong H, Ci X, Li H, Yu L, et al. Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages. Int J Immunopharmacol. 2009;9:354–9.CrossRef
15.
Zurück zum Zitat Zhang X, Song Y, Ci X, An N, Ju Y, Li H, et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res. 2008;57:524–9.PubMedCrossRef Zhang X, Song Y, Ci X, An N, Ju Y, Li H, et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res. 2008;57:524–9.PubMedCrossRef
16.
Zurück zum Zitat Van Rijt LS, Kuipers H, Vos N, Hijdra D, Hoogsteden HC, Lambrecht BN. A rapid flow cytometric method for determining the cellular composition of bronchoalveolar lavage fluid cells in mouse models of asthma. J Immunol Methods. 2004;288:111–21.PubMedCrossRef Van Rijt LS, Kuipers H, Vos N, Hijdra D, Hoogsteden HC, Lambrecht BN. A rapid flow cytometric method for determining the cellular composition of bronchoalveolar lavage fluid cells in mouse models of asthma. J Immunol Methods. 2004;288:111–21.PubMedCrossRef
17.
Zurück zum Zitat Zhou J, Kang Z, Xie Q, Liu C, Lou S, Chen Y, et al. Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig. J Endocrinol. 2003;177:R1–4.PubMedCrossRef Zhou J, Kang Z, Xie Q, Liu C, Lou S, Chen Y, et al. Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig. J Endocrinol. 2003;177:R1–4.PubMedCrossRef
18.
Zurück zum Zitat Pene J, Rousset F, Briere F, Chretien I, Bonnefoy JY, Spits H, et al. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons a, g and prostaglandin E2. Proc Nat Acad Sci USA. 1988;85:6880–4.PubMedCrossRef Pene J, Rousset F, Briere F, Chretien I, Bonnefoy JY, Spits H, et al. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons a, g and prostaglandin E2. Proc Nat Acad Sci USA. 1988;85:6880–4.PubMedCrossRef
19.
Zurück zum Zitat Umetsu DT, DeKruyff RH. TH1 and TH2 CD4+ cells in human allergic diseases. J Allergy Clin Immunol. 1997;100:1–6.PubMedCrossRef Umetsu DT, DeKruyff RH. TH1 and TH2 CD4+ cells in human allergic diseases. J Allergy Clin Immunol. 1997;100:1–6.PubMedCrossRef
20.
Zurück zum Zitat Corry DB, Grunig G, Hadeiba H, Kurup VP, Warnock ML, Sheppard D, et al. Requirementsfor allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol Med. 1998;4:344–55.PubMedCrossRef Corry DB, Grunig G, Hadeiba H, Kurup VP, Warnock ML, Sheppard D, et al. Requirementsfor allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol Med. 1998;4:344–55.PubMedCrossRef
21.
Zurück zum Zitat Curtis JL, Byrd PK, Warnock ML, Kaltreider HB. Requirement of CD4-positive T cells for cellular recruitment to the lungs of mice in response to a particulate intratracheal antigen. J Clin Invest. 1991;88:1244–54.PubMedCrossRef Curtis JL, Byrd PK, Warnock ML, Kaltreider HB. Requirement of CD4-positive T cells for cellular recruitment to the lungs of mice in response to a particulate intratracheal antigen. J Clin Invest. 1991;88:1244–54.PubMedCrossRef
22.
Zurück zum Zitat Kips JC. Cytokines in asthma. Eur Respir J. 2001;18:24–33. Kips JC. Cytokines in asthma. Eur Respir J. 2001;18:24–33.
23.
24.
Zurück zum Zitat Ngoc LP, Gold DR, Tzianabos AO, Weiss ST, Celedon JC. Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol. 2005;5:161–6.PubMedCrossRef Ngoc LP, Gold DR, Tzianabos AO, Weiss ST, Celedon JC. Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol. 2005;5:161–6.PubMedCrossRef
25.
Zurück zum Zitat Wills-Karp M, Luyimbazi J, Xu X, Schofield B. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.PubMedCrossRef Wills-Karp M, Luyimbazi J, Xu X, Schofield B. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.PubMedCrossRef
26.
Zurück zum Zitat Purkerson J, Isakson P. A two-signal model for regulation of immunoglobulin isotype switching. FASEB J. 1992;6:3245–52.PubMed Purkerson J, Isakson P. A two-signal model for regulation of immunoglobulin isotype switching. FASEB J. 1992;6:3245–52.PubMed
27.
Zurück zum Zitat Kimber I, Stone S, Dearman RJ. Assessment of the inherent allergenic potential of proteins in mice. Environ Health Perspect. 2003;111:227–31.PubMedCrossRef Kimber I, Stone S, Dearman RJ. Assessment of the inherent allergenic potential of proteins in mice. Environ Health Perspect. 2003;111:227–31.PubMedCrossRef
28.
Zurück zum Zitat Abu-Ghazaleh RI, Kita H, Gleich GJ. Eosinophil activation and function in health and disease. Immunol Ser. 1992;57:137–67.PubMed Abu-Ghazaleh RI, Kita H, Gleich GJ. Eosinophil activation and function in health and disease. Immunol Ser. 1992;57:137–67.PubMed
29.
Zurück zum Zitat Coffman RL, Seymour BW, Hudak S, Jackson J, Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1898;245:308–10.CrossRef Coffman RL, Seymour BW, Hudak S, Jackson J, Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1898;245:308–10.CrossRef
30.
Zurück zum Zitat Kopf M, Brombacher F, Hodgkin PD, Ramsay AJ, Milbourne EA, Dai WJ, et al. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity. 1996;4:15–24.PubMedCrossRef Kopf M, Brombacher F, Hodgkin PD, Ramsay AJ, Milbourne EA, Dai WJ, et al. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity. 1996;4:15–24.PubMedCrossRef
31.
Zurück zum Zitat Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, et al. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med. 1997;185:2143–56.PubMedCrossRef Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, et al. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med. 1997;185:2143–56.PubMedCrossRef
32.
Zurück zum Zitat Fostera PS, Martinez-Moczygembab M, Hustonb DP, Corry DB. Interleukins-4, -5, and -13: emerging therapeutic targets in allergic disease. Pharmacol Ther. 2002;94:253–64.CrossRef Fostera PS, Martinez-Moczygembab M, Hustonb DP, Corry DB. Interleukins-4, -5, and -13: emerging therapeutic targets in allergic disease. Pharmacol Ther. 2002;94:253–64.CrossRef
33.
Zurück zum Zitat Toelle BG, Peat JK, Salome CM. Toward a definition of asthma for epidemiology. Am Rev Respir Dis. 1992;146:633–7.PubMed Toelle BG, Peat JK, Salome CM. Toward a definition of asthma for epidemiology. Am Rev Respir Dis. 1992;146:633–7.PubMed
34.
Zurück zum Zitat Peat J, Toelle B, Salome C. Predictive nature of bronchial responsiveness and respiratory symptoms in a one year cohort study of Sydney schoolchildren. Eur Respir J. 1993;6:662–9.PubMed Peat J, Toelle B, Salome C. Predictive nature of bronchial responsiveness and respiratory symptoms in a one year cohort study of Sydney schoolchildren. Eur Respir J. 1993;6:662–9.PubMed
35.
Zurück zum Zitat Zhu Z, Homer RJ, Wang Z. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersesretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103:779–88.PubMedCrossRef Zhu Z, Homer RJ, Wang Z. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersesretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103:779–88.PubMedCrossRef
36.
Zurück zum Zitat Flohé L, Brigelius-Flohé R, Saliou C, Traber MG, Packer L. Redox regulation of NF-kappa B activation. Free Radic Biol Med. 1997;22:1115–26.PubMedCrossRef Flohé L, Brigelius-Flohé R, Saliou C, Traber MG, Packer L. Redox regulation of NF-kappa B activation. Free Radic Biol Med. 1997;22:1115–26.PubMedCrossRef
37.
Zurück zum Zitat Vanden Berghe W, Plaisance S, Boone E, De Bosscher K, Schmitz ML, Fiers W. p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappaB p65 transactivation mediated by tumor necrosis factor. J Biol Chem. 1998;273:3285–90.CrossRef Vanden Berghe W, Plaisance S, Boone E, De Bosscher K, Schmitz ML, Fiers W. p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappaB p65 transactivation mediated by tumor necrosis factor. J Biol Chem. 1998;273:3285–90.CrossRef
Metadaten
Titel
Anti-inflammatory effects of ivermectin in mouse model of allergic asthma
verfasst von
Shuhan Yan
Xinxin Ci
Na Chen
Chi Chen
Xiangchao Li
Xiao Chu
Jianhua Li
Xuming Deng
Publikationsdatum
01.06.2011
Verlag
SP Birkhäuser Verlag Basel
Erschienen in
Inflammation Research / Ausgabe 6/2011
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-011-0307-8

Weitere Artikel der Ausgabe 6/2011

Inflammation Research 6/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Frühzeitige HbA1c-Kontrolle macht sich lebenslang bemerkbar

22.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes von Anfang an intensiv BZ-senkend zu behandeln, wirkt sich positiv auf Komplikationen und Mortalität aus – und das offenbar lebenslang, wie eine weitere Nachfolgeuntersuchung der UKPD-Studie nahelegt.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.