Skip to main content
SpringerLink
Log in

Time Course of Endotoxin-Induced Airways’ Inflammation in Healthy Subjects

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Few data are available on the kinetic of the airways’ inflammation induced by inhaled endotoxin in a given subject. The purpose of this study was to evaluate in healthy subjects the time-related endotoxin-induced airways’ inflammation. The cells counts from the induced-sputum were evaluated before, 6 and 24 h, and 7 days after an exposure to 20 mcg inhaled endotoxin, in eight pre-selected volunteers. To avoid interference of the induced-sputum procedure on the response to endotoxin, each time-point was evaluated in randomized order at 2-weeks interval after three separate inhalations of endotoxin. A significant rise of the relative number of lymphocytes (p < 0.05) and polymorphonuclear neutrophils (PMN; p < 0.02) and of the absolute number of PMN (p < 0.05) occurring at 6 h, followed by an increase of the absolute number of the total viable cells (p < 0.01), macrophages (p < 0.001), neutrophils (p < 0.01), and lymphocytes (p < 0.05) at 24 h after endotoxin inhalation. The inflammatory response recovered totally after 7 days. In human beings, the inhalation of endotoxin induced a transient airway inflammation after 6 h, peaked at 24 h and recovered after 7 days. When repeated endotoxin inhalations are used as a model of inflammation, a wash-out period of at least 7 days should be applied between each exposure in each subject.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

REFERENCES

  1. Rylander R, editor (1997) Endotoxins in the environment: a criteria document. Int J Occup Environ Health 3 (suppl 1): S1–S48.

    Google Scholar 

  2. Hasday, J.D., R. Bascom, J.J. Costa, T. Fitzgerald, and W. Dubin. 1999. Bacterial endotoxin is an active component of cigarette smoke. Chest 115: 829–835.

    Article  PubMed  CAS  Google Scholar 

  3. Park, J.-H., D.R. Gold, D.L. Spiegelma, H.A. Burge, and D.K. Milton. 2001. House dust endotoxin and wheeze in the first year of life. American Journal of Respiratory and Critical Care Medicine 163: 322–328.

    PubMed  CAS  Google Scholar 

  4. Thorne, P.S., K. Kulhankova, Yin, R. Cohn, S.J. Arbes, and D.C. Zeldin. 2005. Endotoxin exposure is a risk factor for asthma. American Journal of Respiratory and Critical Care Medicine 172: 1371–1377.

    Article  PubMed  Google Scholar 

  5. Michel, O., J. Kips, J. Duchateau, F. Vertongen, L. Robert, H. Collet, R. Pauwels, and R. Sergysels. 1996. Severity of asthma is related to endotoxin in house dust. American Journal of Respiratory and Critical Care Medicine 154: 1641–1646.

    PubMed  CAS  Google Scholar 

  6. Schwartz, D.A., K.J. Donham, S.A. Olenchock, W.J. Popendorf, D.S. Van Fossen, L.F. Burmeister, and J.A. Merchant. 1995. Determinants of longitudinal changes in spirometric functions among swine confinement operators and farmers. American Journal of Respiratory and Critical Care Medicine 151: 47–53.

    PubMed  CAS  Google Scholar 

  7. Michel, O., R. Ginnani, B. Le Bon, J. Content, R. Sergysels, and J. Duchateau. 1992. Inflammatory response to acute inhalation of endotoxin in asthmatic patients. American Review of Respiratory Disease 146: 352–357.

    PubMed  CAS  Google Scholar 

  8. Nightingale, J.A., D.F. Rogers, L.A. Hart, S.A. Kharitonov, K.F. Chung, and P.J. Barnes. 1998. Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects. Thorax 53: 563–571.

    Article  PubMed  CAS  Google Scholar 

  9. Michel, O., M. Dentener, F. Corazza, W. Buurman, and R. Rylander. 2001. Normal subjects express differences in clinical responses to inhaled lipopolysaccharide wich are related with inflammation and with atopy. The Journal of Allergy and Clinical Immunology 107: 797–804.

    Article  PubMed  CAS  Google Scholar 

  10. Alexis, N.E., M.W. Eldridge, and D.B. Peden. 2003. Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects. The Journal of Allergy and Clinical Immunology 112: 353–361.

    Article  PubMed  CAS  Google Scholar 

  11. Kitz, R., M.A. Rose, K. Placzek, J. Schulze, S. Zielen, and R. Schubert. 2008. LPS inhalation challenge: a new tool to characterize the infammatory response in humans. Medical Microbiology and Immunology 197: 13–19.

    Article  PubMed  CAS  Google Scholar 

  12. Groneberg, D.A., and K.F. Chung. 2004. Models of chronic obstructive pulmonary disease. Respiratory Research 5: 18–34.

    Article  PubMed  Google Scholar 

  13. O’Grady, N.P., H.L. Preas, J. Pugin, C. Fiuza, M. Tropea, D. Reda, S.M. Banks, and A.F. Suffredini. 2001. Local inflammatory responses following bronchial endotoxin instillation in humans. American Journal of Respiratory and Critical Care Medicine 163: 1591–1598.

    PubMed  Google Scholar 

  14. Loh, L.C., B. Vyas, V. Kanabar, D.M. Kemeny, and B.J. O’Connor. 2006. Inhaled endotoxin in healthy human subjects: a dose-related study on systemic effects and peripheral CD4+ and CD8+ T cells. Respiratory Medicine 100: 519–528.

    Article  PubMed  CAS  Google Scholar 

  15. Kline, J.N., J.D. Cowden, G.W. Hunninghake, B.C. Schutte, J.L. Watt, C.L. Wohlford-Lenane, L.S. Powers, M.P. Jones, and D.A. Schwartz. 1999. Variable airway responsiveness to inhaled lipopolysaccharide. American Journal of Respiratory and Critical Care Medicine 160: 297–303.

    PubMed  CAS  Google Scholar 

  16. Michel, O., T.D. LeVan, D. Stern, M. Dentener, J. Thorn, D. Gnat, M.L. Beijer, P. Cochaux, P.G. Holt, F.D. Martinez, and R. Rylander. 2003. Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings. The Journal of Allergy and Clinical Immunology 112: 923–929.

    Article  PubMed  CAS  Google Scholar 

  17. Bland, J.M., and D.G. Altman. 1986. Statistical methods to assessing agreement beween two methods of clinical measurement. Lancet 1(8476): 307–310.

    Article  PubMed  CAS  Google Scholar 

  18. Pavord, I.D., M.M.M. Pizzichini, E. Pizzichini, and F.E. Hargraeve. 1997. The use of induced-sputum to investigate airway inflammation. Thorax 52: 498–501.

    Article  PubMed  CAS  Google Scholar 

  19. van der Vaart, H., D.S. Postma, W. Timens, H.F. Kauffman, M.N. Hylkema, and N.H. Ten Hacken. 2006. Repeated sputum inductions induce a transient neutrophilic and eosinophilic response. Chest 130: 1157–1164.

    Article  PubMed  Google Scholar 

  20. Schwartz, D.A., and D.N. Cook. 2005. Polymorphisms of the Toll-like receptors and human disease. Clinical Infectious Diseases 41(Suppl 7): S403–S407.

    PubMed  CAS  Google Scholar 

  21. Martinez, F.D. 2007. CD14, endotoxin, and asthma risk: actions and interactions. Proceedings of the American Thoracic Society 4: 221–225.

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

P. Dinh Huy Duc is supported by the CUD (Commission Universitaire au Développement).

Conflict of Interest

None.

Author information

Authors and Affiliations

  1. Clinics of Immuno-allergology, CHU Brugmann (Université Libre de Bruxelles–ULB), pl Van Gehuchten, 4, 1020, Brussels, Belgium

    Virginie Doyen, Duc Huy Phong Dinh & Olivier Michel

  2. Clinic of Hematology, CHU Brugmann (Université Libre de Bruxelles–ULB), pl Van Gehuchten, 4, 1020, Brussels, Belgium

    Zaina Kassengera

  3. Department of Immunology, Pham Ngoc Thach University of Medicine (PNTU), Ho Chi Minh City, Vietnam

    Duc Huy Phong Dinh

Authors
  1. Virginie Doyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zaina Kassengera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Duc Huy Phong Dinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olivier Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olivier Michel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doyen, V., Kassengera, Z., Dinh, D.H.P. et al. Time Course of Endotoxin-Induced Airways’ Inflammation in Healthy Subjects. Inflammation 35, 33–38 (2012). https://doi.org/10.1007/s10753-010-9286-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-010-9286-0

KEY WORDS

Search

Navigation