Skip to main content
Top
Published in: Inflammation Research 7/2009

01-07-2009 | Short Communication

Lovastatin inhibits antigen-induced airway eosinophilia without affecting the production of inflammatory mediators in mice

Authors: Y. Chiba, S. Sato, M. Misawa

Published in: Inflammation Research | Issue 7/2009

Login to get access

Abstract

Objective and design

Statins have been proposed as a novel treatment of respiratory diseases. To determine the beneficial effects of statins on allergic bronchial asthma, the effect of systemic treatment with lovastatin on antigen-induced airway inflammation was investigated.

Subjects

Male BALB/c mice were used.

Treatments

Mice were sensitized and repeatedly challenged with ovalbumin (OA) antigen to induce asthmatic response. Animals were also treated with lovastatin (4 mg/kg/day, i.p.) once a day prior to and during the antigen inhalation period.

Methods

Inflammatory cell counts and levels of interleukin (IL)-4, IL-13, eotaxin, thymus and activation-regulated chemokine and leukotriene B4 (LTB4) in bronchoalveolar lavage (BAL) fluids were measured.

Results

Significant increases in eosinophils and levels of the T helper 2 cytokines, chemokines and LTB4 in BAL fluids in association with the increments of total and OA-specific immunoglobulin E (IgE) in sera were observed in the repeatedly antigen-challenged mice. The airway eosinophilia was ameliorated by lovastatin, whereas it had no significant effect on the levels of these inflammatory mediators or IgE.

Conclusion

Lovastatin may be beneficial for the treatment of allergic inflammatory diseases in the airways, such as allergic bronchial asthma.
Literature
1.
go back to reference Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033–9.PubMed Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033–9.PubMed
2.
go back to reference Busse WW, Coffman RL, Gelfand EW, Kay AB, Rosenwasser LJ. Mechanisms of persistent airway inflammation. Am J Respir Crit Care Med. 1995;152:388–93.PubMed Busse WW, Coffman RL, Gelfand EW, Kay AB, Rosenwasser LJ. Mechanisms of persistent airway inflammation. Am J Respir Crit Care Med. 1995;152:388–93.PubMed
3.
go back to reference Lukacs NW, Strieter RM, Kunkel SL. Leukocyte infiltration in allergic airway inflammation. Am J Respir Cell Mol Biol. 1995;13:1–6.PubMedCrossRef Lukacs NW, Strieter RM, Kunkel SL. Leukocyte infiltration in allergic airway inflammation. Am J Respir Cell Mol Biol. 1995;13:1–6.PubMedCrossRef
4.
go back to reference Walker C, Kaegi MK, Braun P, Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol. 1991;88:935–42.PubMedCrossRef Walker C, Kaegi MK, Braun P, Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol. 1991;88:935–42.PubMedCrossRef
5.
go back to reference Tillie-Leblond I, Gosset P, Tonnel A-B. Inflammatory events in severe acute asthma. Allergy. 2005;60:23–9.PubMedCrossRef Tillie-Leblond I, Gosset P, Tonnel A-B. Inflammatory events in severe acute asthma. Allergy. 2005;60:23–9.PubMedCrossRef
6.
go back to reference Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–7.PubMedCrossRef Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–7.PubMedCrossRef
7.
go back to reference Briel M, Studer M, Glass TR, Bucher HC. Effects of statins on stroke prevention in patients with and without coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2004;117:596–606.PubMedCrossRef Briel M, Studer M, Glass TR, Bucher HC. Effects of statins on stroke prevention in patients with and without coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2004;117:596–606.PubMedCrossRef
8.
go back to reference Sun D, Fernandes G. Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production. Cell Immunol. 2003;223:52–62.PubMedCrossRef Sun D, Fernandes G. Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production. Cell Immunol. 2003;223:52–62.PubMedCrossRef
9.
go back to reference McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY. A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma. J Immunol. 2004;172:2903–8.PubMed McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY. A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma. J Immunol. 2004;172:2903–8.PubMed
10.
go back to reference Hothersall E, McSharry C, Thomson NC. Potential therapeutic role for statins in respiratory disease. Thorax. 2006;61:729–34.PubMedCrossRef Hothersall E, McSharry C, Thomson NC. Potential therapeutic role for statins in respiratory disease. Thorax. 2006;61:729–34.PubMedCrossRef
11.
go back to reference Chiba Y, Ueno A, Shinozaki K, Takeyama H, Nakazawa S, et al. Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice. Respir Res. 2005;6:4.PubMedCrossRef Chiba Y, Ueno A, Shinozaki K, Takeyama H, Nakazawa S, et al. Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice. Respir Res. 2005;6:4.PubMedCrossRef
12.
go back to reference Chiba Y, Kurotani R, Kusakabe T, Miura T, Link BW, Misawa M, et al. Uteroglobin-related protein 1 expression suppresses allergic airway inflammation in mice. Am J Respir Crit Care Med. 2006;173:958–64.PubMedCrossRef Chiba Y, Kurotani R, Kusakabe T, Miura T, Link BW, Misawa M, et al. Uteroglobin-related protein 1 expression suppresses allergic airway inflammation in mice. Am J Respir Crit Care Med. 2006;173:958–64.PubMedCrossRef
13.
go back to reference Chiba Y, Arima J, Sakai H, Misawa M. Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2008;294:L705–13.PubMedCrossRef Chiba Y, Arima J, Sakai H, Misawa M. Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2008;294:L705–13.PubMedCrossRef
14.
go back to reference Chiba Y, Sato S, Misawa M. Inhibition of antigen-induced bronchial smooth muscle hyperresponsiveness by lovastatin in mice. J Smooth Muscle Res. 2008;44:123–8.PubMedCrossRef Chiba Y, Sato S, Misawa M. Inhibition of antigen-induced bronchial smooth muscle hyperresponsiveness by lovastatin in mice. J Smooth Muscle Res. 2008;44:123–8.PubMedCrossRef
15.
go back to reference Kwak YG, Song CH, Yi HK, Hwang PH, Kim JS, Lee KS, et al. Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma. J Clin Invest. 2003;111:1083–92.PubMed Kwak YG, Song CH, Yi HK, Hwang PH, Kim JS, Lee KS, et al. Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma. J Clin Invest. 2003;111:1083–92.PubMed
16.
go back to reference Yeh YF, Huang SL. Enhancing effect of dietary cholesterol and inhibitory effect of pravastatin on allergic pulmonary inflammation. J Biomed Sci. 2004;11:599–606.PubMedCrossRef Yeh YF, Huang SL. Enhancing effect of dietary cholesterol and inhibitory effect of pravastatin on allergic pulmonary inflammation. J Biomed Sci. 2004;11:599–606.PubMedCrossRef
17.
go back to reference Romagnani S. Cytokines and chemoattractants in allergic inflammation. Mol Immunol. 2002;38:881–5.PubMedCrossRef Romagnani S. Cytokines and chemoattractants in allergic inflammation. Mol Immunol. 2002;38:881–5.PubMedCrossRef
18.
go back to reference Zimmermann N, Hershey GK, Foster PS, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol. 2003;111:227–42.PubMedCrossRef Zimmermann N, Hershey GK, Foster PS, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol. 2003;111:227–42.PubMedCrossRef
19.
go back to reference Foster PS, Mould AW, Yang M, Mackenzie J, Mattes J, Hogan SP, et al. Elemental signals regulating eosinophil accumulation in the lung. Immunol Rev. 2001;179:173–81.PubMedCrossRef Foster PS, Mould AW, Yang M, Mackenzie J, Mattes J, Hogan SP, et al. Elemental signals regulating eosinophil accumulation in the lung. Immunol Rev. 2001;179:173–81.PubMedCrossRef
20.
go back to reference Miyazaki E, Nureki S, Fukami T, Shigenaga T, Ando M, Ito K, et al. Elevated levels of thymus- and activation-regulated chemokine in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia. Am J Respir Crit Care Med. 2002;165:1125–31.PubMed Miyazaki E, Nureki S, Fukami T, Shigenaga T, Ando M, Ito K, et al. Elevated levels of thymus- and activation-regulated chemokine in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia. Am J Respir Crit Care Med. 2002;165:1125–31.PubMed
21.
go back to reference Miyahara N, Miyahara S, Takeda K, Gelfand EW. Role of the LTB4/BLT1 pathway in allergen-induced airway hyperresponsiveness and inflammation. Allergol Int. 2006;55:91–7.PubMedCrossRef Miyahara N, Miyahara S, Takeda K, Gelfand EW. Role of the LTB4/BLT1 pathway in allergen-induced airway hyperresponsiveness and inflammation. Allergol Int. 2006;55:91–7.PubMedCrossRef
23.
go back to reference van Aelst L, D’Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997;11:2295–322.PubMedCrossRef van Aelst L, D’Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997;11:2295–322.PubMedCrossRef
24.
go back to reference Honing H, van den Berg TK, van der Pol SM, Dijkstra CD, van der Kammen RA, Collard JG, et al. RhoA activation promotes transendothelial migration of monocytes via ROCK. J Leukoc Biol. 2004;75:523–8.PubMedCrossRef Honing H, van den Berg TK, van der Pol SM, Dijkstra CD, van der Kammen RA, Collard JG, et al. RhoA activation promotes transendothelial migration of monocytes via ROCK. J Leukoc Biol. 2004;75:523–8.PubMedCrossRef
25.
go back to reference van Buul JD, Hordijk PL. Signaling in leukocyte transendothelial migration. Arterioscler Thromb Vasc Biol. 2004;24:824–33.PubMedCrossRef van Buul JD, Hordijk PL. Signaling in leukocyte transendothelial migration. Arterioscler Thromb Vasc Biol. 2004;24:824–33.PubMedCrossRef
26.
go back to reference Worthylake RA, Lemoine S, Watson JM, Burridge K. RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol. 2001;154:147–60.PubMedCrossRef Worthylake RA, Lemoine S, Watson JM, Burridge K. RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol. 2001;154:147–60.PubMedCrossRef
27.
go back to reference Samson KT, Minoguchi K, Tanaka A, Oda N, Yokoe T, Yamamoto Y, et al. Inhibitory effects of fluvastatin on cytokine and chemokine production by peripheral blood mononuclear cells in patients with allergic asthma. Clin Exp Allergy. 2006;36:475–82.PubMedCrossRef Samson KT, Minoguchi K, Tanaka A, Oda N, Yokoe T, Yamamoto Y, et al. Inhibitory effects of fluvastatin on cytokine and chemokine production by peripheral blood mononuclear cells in patients with allergic asthma. Clin Exp Allergy. 2006;36:475–82.PubMedCrossRef
28.
go back to reference Kiener PA, Davis PM, Murray JL, Youssef S, Rankin BM, Kowala M. Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors. Int Immunopharmacol. 2001;1:105–18.PubMedCrossRef Kiener PA, Davis PM, Murray JL, Youssef S, Rankin BM, Kowala M. Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors. Int Immunopharmacol. 2001;1:105–18.PubMedCrossRef
29.
go back to reference Fehr T, Kahlert C, Fierz W, Joller-Jemelka HI, Riesen WF, Rickli H, et al. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis. 2004;175:83–90.PubMedCrossRef Fehr T, Kahlert C, Fierz W, Joller-Jemelka HI, Riesen WF, Rickli H, et al. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis. 2004;175:83–90.PubMedCrossRef
30.
go back to reference Umetsu DT, McIntire JJ, Akbari O, Macaubas C, DeKruyff RH. Asthma: an epidemic of dysregulated immunity. Nat Immunol. 2002;3:715–20.PubMedCrossRef Umetsu DT, McIntire JJ, Akbari O, Macaubas C, DeKruyff RH. Asthma: an epidemic of dysregulated immunity. Nat Immunol. 2002;3:715–20.PubMedCrossRef
Metadata
Title
Lovastatin inhibits antigen-induced airway eosinophilia without affecting the production of inflammatory mediators in mice
Authors
Y. Chiba
S. Sato
M. Misawa
Publication date
01-07-2009
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 7/2009
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-009-0043-5

Other articles of this Issue 7/2009

Inflammation Research 7/2009 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.