Skip to main content
SpringerLink
Log in

General Model of Inflammation

  • Original Article
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Dysfunctions in the immune system, due to genetics, disease or environmental factors, can cause bacterial colonization and chronic inflammation. In cystic fibrosis and chronic obstructive pulmonary disease, respiratory infections can initiate inflammation of the airway. We propose a system of nonlinear ordinary differential equations to describe interactions between macrophages, both inflammatory and anti-inflammatory cytokines, and bacteria. Small changes in parameters governing inflammatory cytokine production and macrophage sensitivity to cytokines result in dramatically different model behaviors. When the immune system is functioning properly, a non-aggressive pathogen will not provide a sufficient trigger to initiate chronic inflammation, however, in disease positive feedback of the inflammatory cytokine can induce chronic inflammation even after a bacterial infection has been resolved. In addition, if the macrophage population is more sensitive to inflammatory cytokines small perturbations initiated by bacteria will also lead to chronic inflammation. We have found nonaggressive bacteria are able to initiate chronic inflammation and propose why anti-inflammatory cytokine therapy may not be effective in resolving this inflammation.

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

Similar content being viewed by others

References

  • Abbas, A.K., Lichtman, A.H., Pober, J.S., 2000. Cellular and Molecular Immunology, 4th edn. Saunders, Philadelphia.

    Google Scholar 

  • Aldallal, N., McNaughton, E.E., Manzel, L.J., Richards, A.M., Zabner, J., Ferkol, T.W., Look, D.C., 2002. Inflammatory response in airway epithelial cells isolated from patients with cystic fibrosis. Am. J. Respir. Crit. Care Med. 166, 1248–1256.

    Article  Google Scholar 

  • Bonfield, T.L., Konstan, M.W., Burfeind, P., Panuska, J.R., Hilliard, J.B., Berger, M., 1995. Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. Am. J. Respir. Cell Mol. Biol. 13, 257–261.

    Google Scholar 

  • Costerton, W., Veeh, R., Shirtliff, M., Pasmore, M., Post, C., Ehrlich, G., 2003. The application of biofilm science to the study and control of chronic bacterial infections. J. Clin. Invest. 112(10), 1466–1477.

    Google Scholar 

  • Danese, S., Semeraro, S., Armuzzi, A., Papa, A., Gasbarrini, A., 2006. Biological therapies for inflammatory bowel disease: research drives clinics. Mini Rev. Medicinal Chem. 6(7), 771–784.

    Article  Google Scholar 

  • Day, J., Rubin, J., Vodovotz, Y., Chow, C.C., Reynolds, A., Clermont, G., 2006. A reduced mathematical model of the acute inflammatory response: II. Capturing scenarios of repeated endotoxin administration. J. Theor. Biol. 242, 237–256.

    Article  MathSciNet  Google Scholar 

  • DeRose, V., 2002. Mechanisms and markers of airway inflammation in cystic fibrosis. Eur. Respir. J. 19, 333–340.

    Article  Google Scholar 

  • Ferkol, T.W., Look, D.C., 2001. Chincks in the armor or the airway. Am. J. Respir. Cell Molec. Biol. 25, 11–13.

    Google Scholar 

  • Goldsby, R.A., Kindt, T.J., Kuby, J., Osborne, B.A., 2002. Immunology, 5th edn. Freeman, New York.

    Google Scholar 

  • Janeway, C.A., Travers, P., Walport, M., Shlomchik, M.J., 2005. Immunobiology the Immune System in Health and Disease, 6th edn. Garland Science, New York.

    Google Scholar 

  • Jesaitis, A.J., Franklin, M.J., Berglund, D., Sasaki, M., Lord, C.I., Bleazard, J.B., Duffy, J.E., Beyenal, H., Lewandowski, Z., 2003. Compromised host defense on Pseudomonas aeruginosa biofilms: Characterization of neutrophil and biofilm interactions. J. Immunol. 171, 4329–4339.

    Google Scholar 

  • Kumar, R., Clermont, G., Vodovotz, Y., Chow, C.C., 2004. The dynamics of acute inflammation. J. Theor. Biol. 230, 145–155.

    Article  MathSciNet  Google Scholar 

  • Löfdahl, J.M., Wahlström, J., Sköld, C.M., 2006. Different inflammatory cell pattern and macrophage phenotype in chronic obstructive pulmonary disease patients, smokers and non-smokers. Clin. Exp. Immunol. 145, 428–437.

    Article  Google Scholar 

  • Machen, T.E., 2006. Innate immune response in CF airway epithelia: hyperinflammatory? Am. J. Physiol., Cell Physiol. 291, C218–C230.

    Article  Google Scholar 

  • McCormack, F.X., Whitsett, J.A., 2002. The pulmonary collectins, SP–A and SP–D, orchestrate innate immunity in the lung. J. Clin. Invest. 109(6), 707–712.

    Google Scholar 

  • Mosser, D.M., 2003. The many faces of macrophage activation. J. Leukoc. Biol. 73, 209–212.

    Article  Google Scholar 

  • Muhlbach, M.S., Stewart, P.W., Leigh, M.W., Noah, T.L., 1999. Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. Am. J. Respir. Crit. Care Med. 160, 186–191.

    Google Scholar 

  • Murray, J.D., 1993. Mathematical Biology, 2nd edn. Springer, Berlin.

    MATH  Google Scholar 

  • O’Donnell, R., Breen, D., Wilson, S., Djukanovic, R., 2006. Inflammatory cells in the airways in COPD. Thorax 61, 448–454.

    Article  Google Scholar 

  • Reynolds, A., Rubin, J., Clermont, G., Day, J., Vodovotz, Y., Ermentrout, G.B., 2006. A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation. J. Theor. Biol. 242, 220–236.

    Article  MathSciNet  Google Scholar 

  • Rosell, A., Monsó, E., Soler, M., Torress, F., Angrill, J., Riise, G., Zalacaín, R., Morera, J., Torres, A., 2005. Microbiological determinants of exacerbation in chronic obstructive pulmonary disease. Arch. Intern. Med. 165, 891–897.

    Article  Google Scholar 

  • Thomson, A. (Ed.), 1998. The Cytokine Handbook, 3rd edn. Academic Press, San Diego.

    Google Scholar 

  • Tirouvanziam, R., de Bentzmann, S., Hubeau, C., Hinnrasky, J., Jacquot, J., Péault, B., Puchelle, E., 2000. Inflammation and infection in naive human cystic fibrosis airway grafts. Am. J. Respir. Cell Mol. Biol. 23, 121–127.

    Google Scholar 

  • Tirouvanziam, R., Khazaal, I., Péault, B., 2002. Primary inflammation in human cystic fibrosis small airways. Am. J. Physiol., Lung Cell. Mol. Physiol. 283, L445–L451.

    Google Scholar 

  • Tran, C.L., Jones, A.D., Cullen, R.T., Donaldson, K., 1999. Mathematical modeling of the retention and clearance of low-toxicity particles in the lung. Inhalation Toxicol. 11(12), 1059–1076.

    Article  Google Scholar 

  • Vodovotz, Y., Clermont, G., Chow, C., An, G., 2004. Mathematical models of the acute inflammatory response. Curr. Opin. Crit. Care 10(5), 383–390.

    Article  Google Scholar 

  • West, J.B., 2003. Pulmonary Pathophysiology: The Essentials, 6th edn. Lippincott, Baltimore.

    Google Scholar 

  • Wigginton, J.E., Kirschner, D., 2001. A model to predict cell–mediated immune reulatory mechanisma during humman infection with Mycobacterium tuberculosis. J. Immunol. 1951–1967.

  • Zaman, M.M., Gelrud, A., Junaidi, O., Regan, M.M., Warny, M., Shea, J.C., Kelly, C., O’Sullivan, B.P., Freedman, S.D., 2004. Interleukin 8 secretion from monocytes of subjects heterozygous for the δF508 cystic fibrosis transmembrane conductance regulator gene mutation is altered. Clin. Diagn. Lab. Immunol. 819–824.

Download references

Author information

Authors and Affiliations

  1. Virginia Military Institute, Lexington, VA, 24450, USA

    Meagan C. Herald

Authors
  1. Meagan C. Herald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meagan C. Herald.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herald, M.C. General Model of Inflammation. Bull. Math. Biol. 72, 765–779 (2010). https://doi.org/10.1007/s11538-009-9468-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11538-009-9468-9

Keywords

Search

Navigation