Journal of Biomedical Science

, Volume 11, Issue 5, pp 599–606 | Cite as

Enhancing effect of dietary cholesterol and inhibitory effect of pravastatin on allergic pulmonary inflammation

  • Ya-Fan Yeh
  • Song-Lih Huang
Original Paper


To elucidate the link between the intake of animal fat and asthma, a murine model was developed to examine the effect of dietary cholesterol on pulmonary allergic inflammation. Male C57BL6 mice were fed either a control diet or a diet supplemented with 2% cholesterol. Following sensitization and inhalation exposure to ovalbumin, the bronchoalveolar lavage fluid of mice in the cholesterol group contained higher numbers of eosinophils and elevated levels of IL-5, PGE2, and MCP-1. In addition, dietary cholesterol also resulted in elevated production of IL-4 and IFN-γ by lymphocytes isolated from the lungs. These inflammatory indicators were all significantly correlated with serum cholesterol levels. In contrast to the effect of dietary cholesterol, adding pravastatin to the drinking water significantly reduced eosinophil infiltration and the levels of IL-5, PGE2 and MCP-1 in lavage fluid. Although dietary cholesterol did not alter baseline IL-12 in the lungs, in mice challenged with ovalbumin the IL-12 levels were reduced in the cholesterol group and elevated significantly in the pravastatin group. The results suggest that dietary cholesterol might enhance pulmonary allergic inflammation, possibly involving both nonspecific inflammatory processes and lymphocyte activities.

Key Words

Cholesterol, dietary Pulmonary allergic inflammation Paravastatin Eosinophil infiltration Murine asthma model 


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  1. 1.
    Dykstra M, Cherukuri A, Sohn HW, Tzeng SJ, Pierce SK. Location is everything: Lipid rafts and immune cell signaling. Annu Rev Immunol 21:457–481;2003.Google Scholar
  2. 2.
    Fei G-Z, Huang Y-H, Swedenborg J, Frostegard J. Oxidised LDL modulates immune-activation by an IL-12 dependent mechanism. Atherosclerosis 169:77–85;2003.Google Scholar
  3. 3.
    Gonzalo JA, Lloyd CM, Wen D, Albar JP, Wells TN, Proudfoot A, Martinez AC, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos JC. The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness. J Exp Med 188:157–167;1998.Google Scholar
  4. 4.
    Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407–411;2000.Google Scholar
  5. 5.
    Han KH, Tangirala RK, Green SR, Quehenberger O. Chemokine receptor CCR2 expression and monocyte chemoattractant protein-1-mediated chemotaxis in human monocytes. A regulatory role for plasma LDL. Arterioscler Throm Vasc Biol 18:1983–1991;1998.Google Scholar
  6. 6.
    Huang S-L, Lin K-C, Pan W-H. Dietary factors associated with physician-diagnosed asthma and allergic rhinitis in teenagers — Analysis of the first Nutrition and Health Surveillance in Taiwan. Clin Exp Allergy 301:259–264;2001.Google Scholar
  7. 7.
    Huang S-L, Shiao G-M, Chou P. Association between body mass index and allergy in teenage girls in Taiwan. Clin Exp Allergy 28:323–329;1999.Google Scholar
  8. 8.
    Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 159:28–35;1997.Google Scholar
  9. 9.
    Kalinski P, Schuitemaker JH, Hilkens CM, Kapsenberg ML. Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: The levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol 161:2804–2809;1998.Google Scholar
  10. 10.
    Karpus WJ, Lukacs NW, Kennedy KJ, Smith WS, Hurst SD, Barrett TA. Differential CC chemokine-induced enhancement of T helper cell cytokine production. J Immunol 158:4129–4136;1997.Google Scholar
  11. 11.
    Kita T, Brown MS, Goldstein JL. Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of mice treated with mevinolin, a competitive inhibitor of the reductase. J Clin Invest 66:1094–1100;1980.Google Scholar
  12. 12.
    Klouche M, Gottschling S, Gerl V, Hell W, Husmann M, Dorweiler B, Messner M, Bhakdi S. Atherogenic properties of enzymatically degraded LDL: Selective induction of MCP-1 and cytotoxic effects on human macrophages. Arterioscler Throm Vasc Biol 18:1376–1385;1998.Google Scholar
  13. 13.
    Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 6:1399–1402;2000.Google Scholar
  14. 14.
    Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R, Campbell C, Gracie JA, Liew FY, McInnes IB. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol 170:1524–1530;2003.Google Scholar
  15. 15.
    Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nat Immunol 2:102–107;2001.Google Scholar
  16. 16.
    Morris RH, Price AJ, Tonks A, Jackson SK, Jones KP. Prostaglandin E(2) and tumour necrosis factor-alpha release by monocytes are modulated by phospholipids. Cytokine 12:1717–1719;2000.Google Scholar
  17. 17.
    Okada M, Suzuki A, Mizuno K, Asada Y, Ino Y, Kuwayama T, Tamakoshi K, Mizutani S, Tomoda Y. Effects of 17 beta-estradiol and progesterone on migration of human monocytic THP-1 cells stimulated by minimally oxidized low-density lipoprotein in vitro. Cardiovasc Res 34:529–535;1997.Google Scholar
  18. 18.
    Omata N, Yasutomi M, Yamada A, Iwasaki H, Mayumi M, Ohshima Y. Monocyte chemoattractant protein-1 selectively inhibits the acquisition of CD40 ligand-dependent IL-12-producing capacity of monocyte-derived dendritic cells and modulates Th1 immune response. J Immunol 169:4861–4866;2002.Google Scholar
  19. 19.
    Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, de Waal Malefyt R, Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1183–1186;1999.Google Scholar
  20. 20.
    Rudich SM, Mongini PK, Perez RV, Katznelson S. HMG-CoA reductase inhibitors pravastatin and simvastatin inhibit human B-lymphocyte activation. Transplant Proc 30:992–995;1998.Google Scholar
  21. 21.
    Smits HH, de Jong EC, Schuitemaker JH, Geijtenbeek TB, van Kooyk Y, Kapsenberg ML, Wierenga EA. Intercellular adhesion molecule-1/LFA-1 ligation favors human Th1 development. J Immunol 168:1710–1716;2002.Google Scholar
  22. 22.
    Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 7:687–692;2001.Google Scholar
  23. 23.
    Yeh Y-F, Huang S-L. Dietary cholesterol enhances pulmonary eosinophilic inflammation in a murine model of asthma. Int Arch Allergy Immunol 125:329–334;2001.Google Scholar

Copyright information

© National Science Council 2004

Authors and Affiliations

  • Ya-Fan Yeh
    • 1
    • 3
  • Song-Lih Huang
    • 1
    • 2
  1. 1.Institute of Public HealthNational Yang-Ming UniversityTaipei
  2. 2.Institute of Environmental Health SciencesNational Yang-Ming UniversityTaipei
  3. 3.Department of Health Care AdministrationDiwan College of ManagementTainanTaiwan

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