IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0067419.html
   My bibliography  Save this article

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

Author

Listed:
  • Rami A Namas
  • John Bartels
  • Rosemary Hoffman
  • Derek Barclay
  • Timothy R Billiar
  • Ruben Zamora
  • Yoram Vodovotz

Abstract

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2−/NO3− data from “middle-aged” (6–8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for “young” (2–3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging.

Suggested Citation

  • Rami A Namas & John Bartels & Rosemary Hoffman & Derek Barclay & Timothy R Billiar & Ruben Zamora & Yoram Vodovotz, 2013. "Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-11, July.
  • Handle: RePEc:plo:pone00:0067419
    DOI: 10.1371/journal.pone.0067419
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067419
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0067419&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0067419?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Zhou Yang & Edward C. Norton & Sally C. Stearns, 2003. "Longevity and Health Care Expenditures," The Journals of Gerontology: Series B, The Gerontological Society of America, vol. 58(1), pages 2-10.
    2. Yoram Vodovotz & Marie Csete & John Bartels & Steven Chang & Gary An, 2008. "Translational Systems Biology of Inflammation," PLOS Computational Biology, Public Library of Science, vol. 4(4), pages 1-6, April.
    3. Carl Nathan, 2002. "Points of control in inflammation," Nature, Nature, vol. 420(6917), pages 846-852, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Chari, A.V. & Valli, Elsa, 2021. "The effect of subsidized childcare on the supply of informal care: Evidence from public kindergarten provision in the US," Journal of Health Economics, Elsevier, vol. 77(C).
    2. de Meijer, Claudine & Koopmanschap, Marc & d' Uva, Teresa Bago & van Doorslaer, Eddy, 2011. "Determinants of long-term care spending: Age, time to death or disability?," Journal of Health Economics, Elsevier, vol. 30(2), pages 425-438, March.
    3. Yang, Y., 2014. "Modeling health and mortality dynamics, and their effects on public finance," Other publications TiSEM c0acd15f-e715-46b1-b146-4, Tilburg University, School of Economics and Management.
    4. Cockx, Lara & Francken, Nathalie, 2014. "Extending the concept of the resource curse: Natural resources and public spending on health," Ecological Economics, Elsevier, vol. 108(C), pages 136-149.
    5. Ishizaki, Tatsuro & Imanaka, Yuichi & Oh, Eun-Hwan & Sekimoto, Miho & Hayashida, Kenshi & Kobuse, Hiroe, 2008. "Association between patient age and hospitalization resource use in a teaching hospital in Japan," Health Policy, Elsevier, vol. 87(1), pages 20-30, July.
    6. de Meijer C & Koopmanschap M & Bago d & Uva T & van Doorslaer E, 2009. "Time To Drop Time-To-Death? –Unravelling The Determinants of LTC Spending In The Netherlands," Health, Econometrics and Data Group (HEDG) Working Papers 09/33, HEDG, c/o Department of Economics, University of York.
    7. Cristiane R. S. Câmara & Carlos A. Urrea & Vicki Schlegel, 2013. "Pinto Beans ( Phaseolus vulgaris L.) as a Functional Food: Implications on Human Health," Agriculture, MDPI, vol. 3(1), pages 1-22, February.
    8. Afschin Gandjour, 2009. "Aging diseases – do they prevent preventive health care from saving costs?," Health Economics, John Wiley & Sons, Ltd., vol. 18(3), pages 355-362, March.
    9. Keegan, Conor & Brick, Aoife & Bergin, Adele & Wren, Maev-Ann & Whyte, Richard & Henry, Edward, 2020. "Projections of expenditure for public hospitals in Ireland, 2018–2035, based on the Hippocrates Model," Research Series, Economic and Social Research Institute (ESRI), number RS117.
    10. Edward Norton & Hua Wang & Sally Stearns, 2006. "Behavioral Implications of Out-of-Pocket Health Care Expenditures," Swiss Journal of Economics and Statistics (SJES), Swiss Society of Economics and Statistics (SSES), vol. 142(V), pages 3-11.
    11. Ozbugday, Fatih Cemil & Tirgil, Abdullah & Kose, Elif Gul, 2020. "Efficiency changes in long-term care in OECD countries: A non-parametric Malmquist Index approach," Socio-Economic Planning Sciences, Elsevier, vol. 70(C).
    12. Leena Forma & Mari Aaltonen & Jutta Pulkki & Jani Raitanen & Pekka Rissanen & Marja Jylhä, 2017. "Care service use in 2 years preceding suicide among older adults: comparison with those who died a natural death and those who lived longer," European Journal of Ageing, Springer, vol. 14(2), pages 143-153, June.
    13. Eric French & John Bailey Jones & Elaine Kelly & Jeremy McCauley, 2018. "End-of-Life Medical Expenses," Working Paper 18-18, Federal Reserve Bank of Richmond.
    14. Chloe Allison & Neryvia Pillay, 2024. "Cash transfers and prices what is the impact of social welfare on prices," Working Papers 11057, South African Reserve Bank.
    15. Murphy, Michael & Martikainen, Pekka, 2013. "Use of hospital and long-term institutional care services in relation to proximity to death among older people in Finland," Social Science & Medicine, Elsevier, vol. 88(C), pages 39-47.
    16. Polder, Johan J. & Barendregt, Jan J. & van Oers, Hans, 2006. "Health care costs in the last year of life--The Dutch experience," Social Science & Medicine, Elsevier, vol. 63(7), pages 1720-1731, October.
    17. Gandjour, Afschin & Lauterbach, Karl Wilhelm, 2005. "Does prevention save costs?: Considering deferral of the expensive last year of life," Journal of Health Economics, Elsevier, vol. 24(4), pages 715-724, July.
    18. Norton, E.C., 2016. "Health and Long-Term Care," Handbook of the Economics of Population Aging, in: Piggott, John & Woodland, Alan (ed.), Handbook of the Economics of Population Aging, edition 1, volume 1, chapter 0, pages 951-989, Elsevier.
    19. Warren C. Sanderson & Sergei Scherbov, 2007. "A new perspective on population aging," Demographic Research, Max Planck Institute for Demographic Research, Rostock, Germany, vol. 16(2), pages 27-58.
    20. Li-Fan Liu, 2014. "The Health Heterogeneity of and Health Care Utilization by the Elderly in Taiwan," IJERPH, MDPI, vol. 11(2), pages 1-14, January.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0067419. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.