A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma.

McKay, Anne; Leung, Bernard P; McInnes, Iain B; Thomson, Neil C; Liew, Foo Y

doi:10.4049/jimmunol.172.5.2903

Cited by 309Asthma and respiratory diseasesAllergic Rhinitis and SensitizationIL-33, ST2, and ILC Pathways

A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma.

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McKay, Anne, Leung, Bernard P, McInnes, Iain B, Thomson, Neil C, Liew, Foo Y·2004·The Journal of Immunology

DOI 10.4049/jimmunol.172.5.2903

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Abstract

Statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, are effective serum cholesterol-lowering agents in clinical practice, and they may also have anti-inflammatory properties. Asthma is characterized by chronic eosinophilic inflammation in the airways, which is thought to be regulated by the activity of T lymphocytes. We therefore examined the anti-inflammatory activity of simvastatin in a murine model of allergic asthma. In mice previously sensitized to OVA, simvastatin treatment, either orally or i.p., reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid in response to inhaled OVA challenge. Simvastatin therapy i.p. was also associated with a reduction in IL-4 and IL-5 levels in bronchoalveolar lavage fluid and, at higher doses, a histological reduction in inflammatory infiltrates in the lungs. OVA-induced IL-4, IL-5, IL-6, and IFN-γ secretion was reduced in thoracic lymph node cultures from simvastatin-treated mice. Simvastatin treatment did not alter serum total IgE or OVA-specific IgG1 and IgG2a levels. These data demonstrate the therapeutic potential of statin-sensitive pathways in allergic airways disease.

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Statins have anti-inflammatory and immunomodulatory properties affecting both Th1 and Th2 immune responses.
“Multiple reports indicate that statins have anti-inflammatory and immunomodulatory properties affecting both Th1 and Th2 immune responses (Leung et al., 2003; McKay et al., 2004; Palaniswamy et al., 2010).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as McKay et al., 2004

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Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
OLSSON, A. G., McMurray, J. J. V., Thorgeirsson, G., Spaulding, C. M., Slattery, J., Pyörälà, K., Færgeman, O., Wright, R. S., Berg, K. M., Wilhelmsen, L., et al. (1994) · The Lancet · Cited by 8,467 · see citing works
Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511163332001 · Cited by 7,449 · see citing works
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
SCANDINAVIANSIMVASTATINSURVIVAL (1994) · The Lancet · doi:10.1016/s0140-6736(94)90566-5 · Cited by 3,638 · see citing works
Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic Asthma
Robinson, D. S., Hamid, Q. A., Ying, S., Tsicopoulos, A., Barkans, J. R., Bentley, A. M., Corrigan, C. J., Durham, S. R., & Kay, A. B. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201303260504 · Cited by 2,767 · see citing works
Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease
Tuomilehto, J., Vidgrén, G., Toivanen, L., Tuomilehto‐Wolf, E., Kohtamäki, K., Stengård, J., Zimmet, P., Mackay, I. R., Rowley, M. J., & Koskela, P. U. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92521-6 · Cited by 1,691 · see citing works
Effect of Statin Therapy on C-Reactive Protein Levels
Albert, M. A., Danielson, E., Rifai, N., Ridker, P. M., & for the PRINCE Investigators (2001) · JAMA · doi:10.1001/jama.286.1.64 · Cited by 1,642 · see citing works
Statins as a newly recognized type of immunomodulator.
Kwak, B., Mulhaupt, F., Myit, S., & Mach, F. (2000) · Nature Medicine · doi:10.1038/82219 · Cited by 1,383 · see citing works
Pleiotropic Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors
Takemoto, M., & Liao, J. K. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq1101.098486 · Cited by 1,268 · see citing works
HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway
Dimmeler, S., Aicher, A., Vasa‐Nicotera, M., Mildner-Rihm, C., Adler, K., Tiemann, M., Rütten, H., Fichtlscherer, S., Martin, H., & Zeiher, A. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13152 · Cited by 1,206 · see citing works
The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease
Youssef, S., Stüve, O., Patarroyo, J. C., Ruiz, P. J., Radosevich, J. L., Hur, E. M., Bravo, M., Mitchell, D. J., Sobel, R. A., Steinman, L., et al. (2002) · Nature · doi:10.1038/nature01158 · Cited by 1,094 · see citing works
Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site
Weitz‐Schmidt, G., Welzenbach, K., Brinkmann, V., Kamata, T., Kallen, J. A., Bruns, C., Cottens, S., Takada, Y., & Hommel, U. (2001) · Nature Medicine · doi:10.1038/89058 · Cited by 1,041 · see citing works
HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway
Dimmeler, S., Aicher, A., Vasa‐Nicotera, M., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113152 · Cited by 1,025 · see citing works
Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines
Frostegård, J., Ulfgren, A., Nyberg, P., Hedin, U., Swedenborg, J., Andersson, U., & Hansson, G. K. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00011-8 · Cited by 1,002 · see citing works
Pravastatin Treatment Increases Collagen Content and Decreases Lipid Content, Inflammation, Metalloproteinases, and Cell Death in Human Carotid Plaques
Crisby, M., Fredrikson, G. N., Shah, P. K., Yano, J., Zhu, J., & Nilsson, J. Å. (2001) · Circulation · doi:10.1161/01.cir.103.7.926 · Cited by 999 · see citing works
Inflammatory Mediators of Asthma: An Update
Barnes, P. J., Chung, K. F., & Page, C. P. (1998) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01381-4 · Cited by 712 · see citing works
Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy.
Lassmann, H., Brück, W., & Lucchinetti, C. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(00)01909-2 · Cited by 691 · see citing works
Allergen-specific Th1 cells fail to counterbalance Th2 cell–induced airway hyperreactivity but cause severe airway inflammation
Hansen, G., Berry, G. J., DeKruyff, R. H., & Umetsu, D. T. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5155 · Cited by 629 · see citing works
Asthma: an epidemic of dysregulated immunity
Umetsu, D. T., McIntire, J. J., Akbari, O., Macaubas, C., & DeKruyff, R. H. (2002) · Nature Immunology · doi:10.1038/ni0802-715 · Cited by 601 · see citing works
The role of allergy in the development of asthma
Holt, P. G., Macaubas, C., Stumbles, P. A., & Sly, P. D. (1999) · Nature · doi:10.1038/35037009 · Cited by 472 · see citing works
A novel anti-inflammatory role for simvastatin in inflammatory arthritis.
Leung, B. P., Sattar, N., Crilly, A., Prach, M., McCarey, D. W., Payne, H., Madhok, R., Campbell, C., Gracie, J. A., Liew, F. Y., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1524 · Cited by 434 · see citing works
Self-citation
Simvastatin Has Anti-Inflammatory and Antiatherosclerotic Activities Independent of Plasma Cholesterol Lowering
Sparrow, C. P., Burton, C. A., Hernandez, M., Mundt, S. S., Hassing, H., Patel, S., Rosa, R., Hermanowski‐Vosatka, A., Wang, P.-R., Zhang, D., et al. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.21.1.115 · Cited by 413 · see citing works
Long Term Prevention of Allergic Lung Inflammation in a Mouse Model of Asthma by CpG Oligodeoxynucleotides
Sur, S. A., Wild, J. S., Choudhury, B. K., Sur, N., Alam, R., & Klinman, D. M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.10.6284 · Cited by 382 · see citing works
Feedback Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Livers of Mice Treated with Mevinolin, a Competitive Inhibitor of the Reductase
Kita, T., Brown, M. S., & Goldstein, J. L. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109938 · Cited by 306 · see citing works
Shift toward T lymphocytes with a T helper 1 cytokine‐secretion profile in the joints of patients with rheumatoid arthritis
Dolhain, R. J. E. M., van der Heiden, A. N., ter Haar, N. T., Breedveld, F. C., & Miltenburg, A. M. M. (1996) · Arthritis & Rheumatism · doi:10.1002/art.1780391204 · Cited by 295 · see citing works
Treatment of Relapsing Paralysis in Experimental Encephalomyelitis by Targeting Th1 Cells through Atorvastatin
Aktaş, O., Waiczies, S., Тихоновна, С. А., Dörr, J. R., Seeger, B., Prozorovski, T., Sallach, S., Endres, M., Brocke, S., Nitsch, R., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021425 · Cited by 282 · see citing works
Untitled work
(1997) · PubMed · Cited by 271 · see citing works
T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production
Cohn, L. E., Homer, R., Niu, N., et al. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.9.1309 · Cited by 267 · see citing works
Modulation of Airway Inflammation by Passive Transfer of Allergen-Specific Th1 and Th2 Cells in a Mouse Model of Asthma
Randolph, D. A., Carruthers, C. J. L., Szabo, S. J., et al. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.4.2375 · Cited by 264 · see citing works
Lovastatin inhibits brain endothelial cell Rho‐mediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis
Greenwood, J., Walters, C. E., Pryce, G., Kanuga, N., Bemud, E., Baker, D., & Adamson, P. (2003) · The FASEB Journal · doi:10.1096/fj.02-1014fje · Cited by 227 · see citing works
T helper 2 cells are subject to high dose oral tolerance and are not essential for its induction.
Garside, P., Steel, M., Worthey, E. A., et al. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.11.5649 · Cited by 163 · see citing works
Atherosclerosis and inflammation
Watanabe, T., & Fan, J. (1998) · International Journal of Cardiology · doi:10.1016/s0167-5273(98)00147-8 · Cited by 160 · see citing works
Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors Modify the Inflammatory Response of Human Macrophages and Endothelial Cells Infected With Chlamydia pneumoniae
Kothe, H., Dalhoff, K., Rupp, J., Müller, A., Kreuzer, J., Maass, M., & Katus, H. A. (2000) · Circulation · doi:10.1161/01.cir.101.15.1760 · Cited by 151 · see citing works
Antiinflammatory and Antiarteriosclerotic Actions of HMG-CoA Reductase Inhibitors in a Rat Model of Chronic Inhibition of Nitric Oxide Synthesis
Ni, W., Egashira, K., Kataoka, C., Kitamoto, S., Koyanagi, M., Inoue, S., & Takeshita, A. (2001) · Circulation Research · doi:10.1161/hh1701.096614 · Cited by 129 · see citing works
Similar Effects of Atorvastatin, Simvastatin and Pravastatin on Thrombogenic and Inflammatory Parameters in Patients with Hypercholesterolemia
Joukhadar, C., Klein, N., Prinz, M., Schrolnberger, C., Vukovich, T., Wolzt, M., Dorner, G. T., & Schmetterer, L. F. (2001) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1612902 · Cited by 116 · see citing works
The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma
Gauvreau, G. M., Becker, A. B., Boulet, L., et al. (2003) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2003.1689 · Cited by 100 · see citing works
Recombinant Human Platelet-Activating Factor- Acetylhydrolase Inhibits Airway Inflammation and Hyperreactivity in Mouse Asthma Model
Henderson, W. R., Lu, J., Poole, K. M., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.6.3360 · Cited by 77 · see citing works
Transduction of a dominant-negative H-Ras into human eosinophils attenuates extracellular signal–regulated kinase activation and interleukin-5–mediated cell viability
Hall, D. J., Cui, J., Bates, M. E., Stout, B. A., Koenderman, L., Coffer, P. J., & Bertics, P. J. (2001) · Blood · doi:10.1182/blood.v98.7.2014 · Cited by 74 · see citing works
Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 4. Structure−Activity Relationship of Substituents on the Benzene Ring of the Cinnamide
Winn, M., Reilly, E. B., Liu, G., et al. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm0103108 · Cited by 59 · see citing works
Phenotypic Analysis of Airway Eosinophils and Lymphocytes in a Th-2-Driven Murine Model of Pulmonary Inflammation
Watkins, A., Hatfield, C. A., Fidler, S. F., Winterrowd, G. E., Brashler, J. R., Sun, F. F., Taylor, B. M., Vonderfecht, S. L., Conder, G. A., Holgate, S. T., et al. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.15.1.8679219 · Cited by 25 · see citing works
Activation of CD4 T cells by Raf-independent effectors of Ras
Czyzyk, J. K., Brogdon, J. L., Badou, A., Henegariu, O., Preston‐Hurlburt, P., Flavell, R. A., & Bottomly, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031494100 · Cited by 19 · see citing works

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Authors: McKay, A., Leung, B. P., McInnes, I. B., Thomson, N. C., & Liew, F. Y.
Affiliations: University of Glasgow (GB)
Glasgow Royal Infirmary (GB)
Corresponding author: McKay, Anne
ORCID: Leung, Bernard P
McInnes, Iain B
Thomson, Neil C
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2004-03-01
Volume: 172
Issue: 5
Pages: 2903-2908
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.172.5.2903
OpenAlex: W1509483174
Cited by: 309
References: 40
Citations by year: 2026: 1 · 2025: 6 · 2024: 14 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 6 · 2016: 15 · 2015: 14 · 2014: 20 · 2013: 25 · 2012: 17
FWCI: 10.85
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
University of Glasgow
Medical Research Council
Topics: Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: simvastatin, statins, allergic asthma, anti-inflammatory activity, eosinophilic airway inflammation, ovalbumin sensitization, IL-4, IL-5, interleukin-6, interferon-gamma, T cells, bronchoalveolar lavage, IgE, airway inflammation
MeSH terms: Administration, Oral, Allergens, Animals, Anti-Inflammatory Agents, Non-Steroidal, Epitopes, Asthma, Bronchoalveolar Lavage Fluid, Cells, Cultured, Disease Models, Animal, Eosinophilia, Female, Injections, Intraperitoneal, Lymph Nodes, Mice, Inbred BALB C, Ovalbumin, Cytokines, Th2 Cells, Simvastatin, Mice

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A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma.

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