Skip to main content

Advertisement

SpringerLink
Log in

LPS inhalation challenge: a new tool to characterize the inflammatory response in humans

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Inhaling bacterial endotoxin and its derivative LPS can induce a distinct inflammatory response, varying among hosts. Experimental LPS-inhalation is an established procedure in inflammation research. We evaluated experimental LPS-inhalation in 20 young healthy volunteers to determine the safety and the reproducibility of markers of inflammation and clinical findings (symptoms, lung function, exhalative NO, and body temperature). LPS was increased every 30 min up to cumulative 100 μg, the protocol was repeated after 2, 4, and 6 weeks. During 71 provocations, 13 episodes of clinical complaints were observed in 10 subjects. Those were a total of 11 local reactions (15.5%, e.g., cough), and six systemic reactions (8.5%, e.g., fatigue). All adverse events resolved spontaneously within 10 h. Changes of FEV1 and eNO showed no significant differences between the four visits. In the majority of our subjects (88.2% on visit 1–3, 76.5% on visit 4), a rise in body temperature (>0.5°C) was recorded and normalised latest after 24 h. On the first and the last visit, serum concentrations of CrP and LBP increased significantly and correlated well with each other (r = 0.71; P < 0.001). LPS-challenge is a safe and tolerable tool to investigate inflammatory response in humans and could lead to better characterization of patients with chronic inflammatory disease.

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
Fig. 4

Similar content being viewed by others

Abbreviations

LPS:

Lipopolysaccharide

LBP:

Lipopolysaccharide binding protein

FEV1 :

Forced expiratory volume within one second

eNO:

exhaled nitric oxide

References

  1. Ahmed N, Thorley R, Xia SY, Samols D, Webster RO (1996) Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis. Am J Respir Crit Care Med 153:1141–1147

    PubMed  CAS  Google Scholar 

  2. Alexis N, Elridge M, Reed W, Bromberg P, Peden DB (2001) CD14-dependent airway neutrophil response to inhaled LPS: role of atopy. J Allergy Clin Immunol 107:31–35

    Article  PubMed  CAS  Google Scholar 

  3. American Thoracic Society (1999) Recommendations for standardized procedures for the online and offline measurements of exhaled lower respiratory nitric oxide and nasal oxide in adults and children. Am J Resp Crit Care Med 160:2104–2117

    Google Scholar 

  4. Bland JM, Altoona DG (1986) Statistical methods for assessing agreement between two methods of clinical measurements. Lancet 1:307–310

    PubMed  CAS  Google Scholar 

  5. Brass DM, Savov JD, Whitehead GS, Maxwell AB, Schwartz DA (2004) LPS binding protein is important in the airway response to inhaled endotoxin. J Allergy Clin Immunol 114:586–592

    Article  PubMed  CAS  Google Scholar 

  6. Fan MH, Klein RD, Steinstraesser L, Merry AC, Nemzek JA et al (2002) An essential role for lipopolysaccharide-binding protein in pulmonary innate immune responses. Shock 18:248–254

    Article  PubMed  Google Scholar 

  7. Fearon DT, Locksley RM (1996) The instructive role of innate immunity in the acquired immune response. Science 272:50–53

    Article  PubMed  CAS  Google Scholar 

  8. Jack RS, Fan X, Bernheiden M, Rune G, Ehlers M, Weber A, Kirsch G, Mentel R, Furll B, Freudenberg M et al (1997) Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature 389:742–745

    Article  PubMed  CAS  Google Scholar 

  9. Jagielo PJ, Thorne PS, Watt JL, Frees KL, Quinn TJ et al (1996) Grain dust and endotoxin inhalation challenges produce similar inflammatory responses in normal subjects. Chest 110:263–270

    PubMed  CAS  Google Scholar 

  10. Kitz R, Rose MA, Borgmann A, Schubert R, Zielen S (2006) Systemic and bronchial inflammation following LPS inhalation in asthmatic and healthy subjects. J Endotox Res 12(6):368–374

    Google Scholar 

  11. Kline JN, Cowden JD, Hunninghake GW, Schutte BC, Watt JL et al (1999) Variable airway responsiveness to inhaled lipopolysaccharide. Am J Respir Crit Care Med 160:297–303

    PubMed  CAS  Google Scholar 

  12. Knapp S, de Vos AF, Florquin S, Golenbock DT, van der Poll T (2003) Lipopolysaccharide binding protein is an essential component of the innate immune response to Escherichia coli peritonitis in mice. Infect Immun 71:6747–6753

    Article  PubMed  CAS  Google Scholar 

  13. Larsson KA, Eklund AG, Hansson LO, Isaksson BM, Malmberg PO (1994) Swine dust causes intense airways inflammation in healthy subjects. Am J Respir Crit Care Med 150:973–977

    PubMed  CAS  Google Scholar 

  14. Mattsby I, Rylander R (1978) Clinical and immunological findings in workers exposed to sewage dust. J Occup Med 20:690–692

    PubMed  CAS  Google Scholar 

  15. Medzhitov R, Janeway CA Jr (1997) Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 9:4–9

    Article  PubMed  CAS  Google Scholar 

  16. Michel O, Dentener M, Corazza F, Buurman W, Rylander R (2001) Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy. J Allergy Clin Immunol 107(5):797–804

    Article  PubMed  CAS  Google Scholar 

  17. Michel O, Ginanni, Sergysels R (1992) Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine. Thorax 47:288–291

    Article  PubMed  CAS  Google Scholar 

  18. Michel O, Kips J, Duchateau J, Vertongen F, Robert L et al (1996) Severity of asthma is related to endotoxin in house dust. Am J Respir Crit Care Med 154(6):1641–1646

    PubMed  CAS  Google Scholar 

  19. Michel O, Nagy AM, Schroeven M, Duchateau J, Nève J et al (1997) Dose-response relationship to inhaled endotoxin in normal subjects. Am J Respir Crit Care Med 156:1157–1164

    PubMed  CAS  Google Scholar 

  20. Michel O, Duchateau J, Plat G, Cantinieaux B, Hotimsky A et al (1995) Blood inflammatory response to inhaled endotoxin in normal subjects. Clin Exp Allergy 25:73–79

    Article  PubMed  CAS  Google Scholar 

  21. Nightingale JA, Rogers DF, Hart LA, Kharitonov SA, Chung KF et al (1998) Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects. Thorax 53:563–571

    PubMed  CAS  Google Scholar 

  22. Rylander R, Bake B, Fischer JJ, Helander IM (1989) Pulmonary function and symptoms after inhalation of endotoxin. Am Rev Resp Dis 140:981–986

    PubMed  CAS  Google Scholar 

  23. Schmitt-Grohé S, Hippe V, Igel M, von Bergmann K, Zielen S et al (2005) Lipopolysaccharide binding protein, cytokine production in whole blood, and lipoproteins in cystic fibrosis. Pediatr Res 58(5):903–907

    Article  PubMed  Google Scholar 

  24. Sundy JS, Wood WA, Watt JL, Kline JN, Schwartz DA (2006) Safety of incremental inhale lipopolysaccharide challenge in humans. J Endotox Res 12(2):113–119

    CAS  Google Scholar 

  25. Thorn J, Rylander R (1998) Inflammatory response after inhalation of bacterial endotoxin assessed by the induced sputum technique. Thorax 53:1047–1052

    Article  PubMed  CAS  Google Scholar 

  26. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431–1433

    Article  PubMed  CAS  Google Scholar 

  27. Zweigner J, Gramm HJ, Singer OC, Wegscheider K, Schumann RR (2001) High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes. Blood 98:3800–3808

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Competing interests: no financial or non-financial interests

Author information

Authors and Affiliations

  1. Children’s Hospital, Department of Pulmonology/Allergology, Frankfurt University, Frankfurt, Germany

    Richard Kitz, Markus A. Rose, Katja Placzek, Johannes Schulze, Stefan Zielen & Ralf Schubert

  2. Children’s Hospital, University of Frankfurt, Allergology/Pulmonology and Cystic Fibrosis, Theodor Stern Kai 7, Frankfurt, 60590, Germany

    Markus A. Rose

Authors
  1. Richard Kitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus A. Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katja Placzek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johannes Schulze
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Zielen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ralf Schubert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Markus A. Rose.

Additional information

Richard Kitz and Markus A. Rose contributed equally and should therefore, be considered as first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kitz, R., Rose, M.A., Placzek, K. et al. LPS inhalation challenge: a new tool to characterize the inflammatory response in humans. Med Microbiol Immunol 197, 13–19 (2008). https://doi.org/10.1007/s00430-007-0053-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-007-0053-2

Keywords

Search

Navigation