, Volume 182, Issue 3, pp 163–171 | Cite as

Lung Inflammatory Responses and Hyperinflation Induced by an Intratracheal Exposure to Lipopolysaccharide in Rats

  • Anne-Helene Jansson
  • Christina Eriksson
  • Xiangdong WangEmail author


Exposure of the respiratory tract to lipopolysaccharide (LPS) induces acute local inflammation and tissue injury associated with the various deliveries of LPS. To determine potential association of local inflammatory responses with respiratory tract dysfunction, infiltration of inflammatory cells, production of inflammatory mediators, lung hyperinflation and edema were measured in Wister rats 2, 4, and 24 h after an intratracheal administration of LPS at different doses (5, 50, 500 and 5000 μg/ml/kg). Lung hyperinflation determined by an increased excised lung gas volume was significantly increased 2 and 4 h after LPS instillation and lung edema occurred from 2 h onward. Peak BAL levels of TNFα appeared at 2 h, MCP-1 at 4 h, and IL-6 at 2 and 4 h, while BAL levels of IL-1β were increased during 24 h after the intratracheal instillation of LPS. Neutrophilia in BAL fluid was noted from 2 h post-challenge. Our results demonstrate a clear dose-related change in the lung weight at 4 and 24 h, in the BAL levels of MCP-1 at 4 h, and IL-6 and IL-1β at 2 and 4 h. It seems important to understand polymorphisms of LPS-induced lung hyperinflation and inflammation. Lung hyperinflation and inflammation may be independent during the development of acute lung injury.


Lipopolysaccharide Airway hyperresponsiveness ELGV Lung injury Cytokines 



The authors thank Senior Information Scientist, Man So, for support of information delivery.


  1. 1.
    Blackwell, TS, Lancaster, LH, Blackwell, TR, Venkatakrishnan, A, Christman, JW 1999Chemotactic gradients predict neutrophilic alveoblitis in endotoxin-treated ratsAm J Respir Crit Care Med15916441652PubMedGoogle Scholar
  2. 2.
    Brigham, KL, Meyrick, B 1986Endotoxin and lung injuryAm Rev Respir Dis133913927PubMedGoogle Scholar
  3. 3.
    Chignard, M, Balloy, V 2000Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharideAm J Physiol Lund Cell Mol Physiol279L10831090Google Scholar
  4. 4.
    Gattinoni, L, Bombino, M, Pelosi, P, Lissoni, A, Pesenti, A, Fumagalli, R, Tagliabue, M 1994Lung structure and function in different stages of severe adult respiratory distress syndromeJAMA27117721779CrossRefPubMedGoogle Scholar
  5. 5.
    Ghosh, S, Latimer, RD, Gray, BM, Harwood, RJ, Oduro, A 1993Endotoxin-induced organ injuryCrit Care Med21S1924PubMedGoogle Scholar
  6. 6.
    Haddad, el-B, McCluskie, K, Birrell, MA,  et al. 2002Differential effects of ebselen on neutrophil recruitment, chemokine, and inflammatory mediator expression in a rat model of lipopolysaccharide-induced pulmonary inflammationJ Immunol169974982PubMedGoogle Scholar
  7. 7.
    Hudson, LD, Steinberg, KP 1999Epidemiology of acute lung injury and ARDSChest11674S82SCrossRefGoogle Scholar
  8. 8.
    Kagari, T, Doi, H, Shimozato, T 2002The importance of IL-1 beta and TNF-alpha, and the noninvolvement of IL-6, in the development of monoclonal antibody-induced arthritisJ Immunol16914591466PubMedGoogle Scholar
  9. 9.
    Lefort, J, Motreff, L, Vargraftig, BB 2001Airway administration of Escherichia coli endotoxin to mice induces glucocorticosteroid-resistant bronchoconstriction and vesopermeationAm J Respir Cell Mol Biol24345351PubMedGoogle Scholar
  10. 10.
    Lefort, J, Singer, M, Leduc, D,  et al. 1998Systemic administration of endotoxin induces bronchopulmonary hyperreactivity dissociated from TNFα formation and neutrophil recruitment into the mouse lungsJ Immunol161474480PubMedGoogle Scholar
  11. 11.
    Luhr, OR, Antonsen, K, Karlsson, M, Aardal, S, Thorsteinsson, A, Frostell, CG, Bonde, J 1999Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark and IcelandAm J Respir Crit Care Med15918491861PubMedGoogle Scholar
  12. 12.
    Michel, O, Kips, J, Duchateua, J, Vertongen, F, Robert, L, Collet, H, Pauwels, R, Sergysels, R 1996Severity of asthma is related to endotoxin in house dustAm J Respir Crit Care Med15416411646PubMedGoogle Scholar
  13. 13.
    Moreland, JG, Fuhrman, RM, Wohlford-Lenane, CL, Quinn, TJ, Benda, E, Pruessner, JA, Schwartz, DA 2001TNF-alpha and IL-1 beta are not essential to the inflammatory response in LPS-induced airway diseaseAm J Physiol Lung Cell Mol Physiol280L173180PubMedGoogle Scholar
  14. 14.
    Rylander, R 2002Endotoxin in the environment–exposure and effectsJ Endotoxin Res8241252CrossRefPubMedGoogle Scholar
  15. 15.
    Sato, K, Kadiiska, MB, Ghio, AJ, Corbett, J, Fann, YC, Holland, SM, Thurman, RG, Mason, RP 2002 In vivo lipid-derived free radical formation by NADPH oxidase in acute lung induced by lipopolysaccharide: a model for ARDSFASEB J1617131720CrossRefPubMedGoogle Scholar
  16. 16.
    Schwartz, DA, Christ, WJ, Kleeberger, SR, Wohlford-Lenane, CL 2001Inhibition of LPS-induced airway hyperresponsiveness and airway inflammation by LPS antagonistsAm J Physiol Lung Cell Mol Physiol280L771778PubMedGoogle Scholar
  17. 17.
    Stengel, PW, Yiamouyiannis, CA, Obenchan, RL, Cockerham, SL, Sibaugh, SA 1995Methacholine-induced pulmonary gas trapping in guinea pigs, hamsters, mice, and ratsJ Appl Physiol7921482153PubMedGoogle Scholar
  18. 18.
    Tasaka, S, Hasegawa, N, Ishizaka, A 2002Pharmacology of acute lung injuryPul Pharm Therap158395CrossRefGoogle Scholar
  19. 19.
    Thorn, J 2001The inflammatory response in humans after inhalation of bacterial endotoxin: a reviewInflam Res50254261CrossRefGoogle Scholar
  20. 20.
    Tobias, PS, Mathison, J, Mintz, D, Lee, JD, Kravchenko, V, Kato, K, Pugin, J, Ulevitch, RJ 1992Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activationAm J Respir Cell Mol Biol7239245PubMedGoogle Scholar
  21. 21.
    Uhlig, S, Brasch, F, Wollin, L, Fehrenbach, H, Richter, J, Wendel, A 1995Functional and fine structural changes in isolated rat lungs challenged with endotoxin ex vivo and in vitro Am J Pathol14612351247PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Anne-Helene Jansson
    • 1
  • Christina Eriksson
    • 1
  • Xiangdong Wang
    • 1
    Email author
  1. 1.Department of Biological SciencesLundSweden

Personalised recommendations