Skip to main content

Advertisement

SpringerLink
Log in

Serum profile of pro- and anti-inflammatory cytokines in rats following implantation of low-temperature plasma-modified titanium plates

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Surface modification of Titanium (Ti) by low-temperature plasma influences cell-material interactions. Therefore, this study aimed at examining serum cytokine levels and associations after intramuscular implantation (n = 8 rats/group) of Ti-plates with Plasma Polymerized Allyl Amine (Ti-PPAAm), Plasma Polymerized Acrylic Acid (Ti-PPAAc), and without such layers (Ti-Controls). Pro-inflammatory (IL-2, IFNγ, IL-6) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were measured weekly for 56 days. Ti-PPAAm caused increased IL-2 (d7-14, d35), increased IFNγ (d35) and decreased IL-10 (d35, d49-56). Ti-PPAAc induced divergent anti-inflammatory cytokine changes with increased IL-4 (d28-56) and decreased IL-10 (d42-56). Ti-Controls elicited increased IL-2 (d42) and IFNγ (d35-42, d56). IL-6 was not detected and IL-13 only in three samples, thus they do not influence the response against these Ti implants. Correlation analysis revealed surface-dependent associations between cytokines indicating the involvement of different inflammatory cell populations. Concluding, different plasma modifications induce specific serum cytokine profiles and associations indicating distinct inflammatory responses.

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

  1. Esposito M. Titanium for dental applications. In: Brunette DM, Tengvall P, Textor M, Thomsen P, editors. Titanium in medicine. Berlin: Springer; 2001. p. 172–230.

    Google Scholar 

  2. Finke B, Lüthen F, Schröder K, Mueller PD, Bergemann C, Frant M, Ohl A, Nebe BJ. Positively charged plasma polymerized titanium boosts osteoblastic focal contact formation in the initial adhesion phase. Biomaterials. 2007;28:4521–34.

    Article  CAS  Google Scholar 

  3. Schröder K, Finke B, Ohl A, Lüthen F, Bergemann C, Nebe B, Rychly J, Walschus U, Schlosser M, Liefeith K, Neumann HG, Weltmann KD. Capability of differently charged plasma polymer coatings for control of tissue interactions with titanium surfaces. J Adhes Sci Technol. 2010;24:1191–205.

    Article  Google Scholar 

  4. Xia Z, Triffitt T. A review on macrophage responses to biomaterials. Biomed Mater. 2006;1:R1–9.

    Article  CAS  Google Scholar 

  5. Davis C, Fischer J, Ley K, Sarembock IJ. The role of inflammation in vascular injury and repair. J Thromb Haemost. 2003;1:1699–709.

    Article  CAS  Google Scholar 

  6. Rodriguez A, Voskerician G, Meyerson H, Macewan SR, Anderson JM. T cell subset distributions following primary and secondary implantation at subcutaneous biomaterial implant sites. J Biomed Mater Res A. 2008;85:556–65.

    Google Scholar 

  7. Goodman SB. Wear particles, periprosthetic osteolysis and the immune system. Biomaterials. 2007;28:5044–8.

    Article  CAS  Google Scholar 

  8. Wang C, Lennartz MR, Loegering DJ, Stenken JA. Multiplexed cytokine detection of interstitial fluid collected from polymeric hollow tube implants—a feasibility study. Cytokine. 2008;43:15–9.

    Article  CAS  Google Scholar 

  9. Schutte RJ, Xie L, Klitzman B, Reichert WM. In vivo cytokine-associated responses to biomaterials. Biomaterials. 2009;30:160–8.

    Article  CAS  Google Scholar 

  10. Rodriguez A, Meyerson H, Anderson JM. Quantitative in vivo cytokine analysis at synthetic biomaterial implant sites. J Biomed Mater Res A. 2009;89:152–9.

    Google Scholar 

  11. Pereira-Lucena CG, Artigiani-Neto R, Lopes-Filho GJ, Frazao CV, Goldenberg A, Matos D, Linhares MM. Experimental study comparing meshes made of polypropylene, polypropylene + polyglactin and polypropylene + titanium: inflammatory cytokines, histological changes and morphometric analysis of collagen. Hernia. 2010;14:299–304.

    Article  CAS  Google Scholar 

  12. Gallo J, Mrazek F, Petrek M. Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study. BMC Med Genet. 2009;10:109.

    Article  Google Scholar 

  13. Smith KA. IL-2. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference: a compendium of cytokines and other mediators of host defense. San Diego: Academic Press; 2001. p. 113–25.

    Google Scholar 

  14. Billiau A, Vandenbroeck K. IFNγ. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference: a compendium of cytokines and other mediators of host defense. San Diego: Academic Press; 2001. p. 641–88.

    Google Scholar 

  15. Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Ann Rev Immunol. 2009;27:451–83.

    Article  CAS  Google Scholar 

  16. Billiau A, Matthys P. Interferon-γ: a historical perspective. Cytokine Growth Factor Rev. 2009;20:97–113.

    Article  CAS  Google Scholar 

  17. Matsuda T, Hirano T. IL-6. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference: a compendium of cytokines and other mediators of host defense. San Diego: Academic Press; 2001. p. 537–63.

    Google Scholar 

  18. Keegan AD. IL-4. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference: a compendium of cytokines and other mediators of host defense. San Diego: Academic Press; 2001. p. 127–35.

    Google Scholar 

  19. RdW Malefyt. IL-10. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference: a compendium of cytokines and other mediators of host defense. San Diego: Academic Press; 2001. p. 165–85.

    Google Scholar 

  20. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226:205–18.

    Article  CAS  Google Scholar 

  21. Kou PM, Babensee JE. Macrophage and dendritic cell phenotypic diversity in the context of biomaterials. J Biomed Mater Res A. 2011;96:239–60.

    Google Scholar 

  22. McKenzie ANJ, Matthews DJ. IL-13. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference: a compendium of cytokines and other mediators of host defense. San Diego: Academic Press; 2001. p. 203–11.

    Google Scholar 

  23. Wynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425–56.

    Article  CAS  Google Scholar 

  24. Finke B, Schröder K, Ohl A. Structure retention and water stability of microwave plasma polymerized films from allylamine and acrylic acid. Plasma Process Polym. 2009;6:S70–4.

    Article  CAS  Google Scholar 

  25. Hoene A, Walschus U, Patrzyk M, Finke B, Lucke S, Nebe B, Schröder K, Ohl A, Schlosser M. In vivo examination of the inflammatory response against allylamine plasma polymer coated titanium implants in a rat model. Acta Biomater. 2010;6:676–83.

    Article  CAS  Google Scholar 

  26. Marfaing-Koka A, Maravic M, Humbert M, Galanaud P, Emilie D. Contrasting effects of IL-4, IL-10 and corticosteroids on RANTES production by human monocytes. Int Immunol. 1996;8:1587–94.

    Article  CAS  Google Scholar 

  27. Terres G, Coffman RL. The role of IL-4 and IL-10 cytokines in controlling an anti-tumor response in vivo. Int Immunol. 1998;10:823–32.

    Article  CAS  Google Scholar 

  28. Specht S, Volkmann L, Wynn T, Hoerauf A. Interleukin-10 (IL-10) counterregulates IL-4-dependent effector mechanisms in Murine Filariasis. Infect Immun. 2004;72:6287–93.

    Article  CAS  Google Scholar 

  29. Baldwin L, Hunt JA. Host inflammatory response to NiCr, CoCr and Ti in a soft tissue implantation model. J Biomed Mater Res A. 2006;79:574–81.

    CAS  Google Scholar 

  30. Wang JY, Wicklund BH, Gustilo RB, Tsukayama DT. Prosthetic metals impair murine immune response and cytokine release in vivo and in vitro. J Orthop Res. 1997;15:688–99.

    Article  CAS  Google Scholar 

  31. Suska F, Gretzer C, Esposito M, Emanuelsson L, Wennerberg A, Tengvall P, Thomsen P. In vivo cytokine secretion and NF-kB activation around titanium and copper implants. Biomaterials. 2005;26:519–27.

    Article  CAS  Google Scholar 

  32. Sauma D, Michea P, Lennon-Duménil AM, Fierro A, Morales J, Rosemblatt M, Bono MR. Interleukin-4 selectively inhibits interleukin-2 secretion by lipopolysaccharide-activated dendritic cells. Scand J Immunol. 2004;59:183–9.

    Article  CAS  Google Scholar 

  33. Tanaka T, Hu-Li J, Seder RA, Fazekas de St Groth B, Paul WE. Interleukin 4 suppresses interleukin 2 and interferon gamma production by naive T cells stimulated by accessory cell-dependent receptor engagement. Proc Natl Acad Sci USA. 1993;90:5914–8.

    Article  CAS  Google Scholar 

  34. Morris SC, Orekhova T, Meadows MJ, Heidorn SM, Yang J, Finkelman FD. IL-4 induces in vivo production of IFN-gamma by NK and NKT cells. J Immunol. 2006;176:5299–305.

    CAS  Google Scholar 

  35. Taga K, Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol. 1992;148:1143–8.

    CAS  Google Scholar 

  36. Mehrotra PT, Donnelly RP, Wong S, Kanegane H, Geremew A, Mostowski HS, Furuke K, Siegel JP, Bloom ET. Production of IL-10 by human natural killer cells stimulated with IL-2 and/or IL-12. J Immunol. 1998;160:2637–44.

    CAS  Google Scholar 

  37. D’Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med. 1993;178:1041–8.

    Article  Google Scholar 

  38. Nicoletti F, Marco RD, Patti F, Nicoletti A, Leonardi C, Reggio E, Meroni P, Reggio A. The antiinflammatory cytokine interleukin-13 is not detectable in the circulation of multiple sclerosis patients and is not inducible by interferon-beta1b treatment, that neither modifies its ex vivo secretion from peripheral blood mononuclear cells. Autoimmunity. 2000;32:265–70.

    Article  CAS  Google Scholar 

  39. van der Poll T, de Waal Malefyt R, Coyle SM, Lowry SF. Antiinflammatory cytokine responses during clinical sepsis and experimental endotoxemia: sequential measurements of plasma soluble interleukin (IL)-1 receptor type II, IL-10, and IL-13. J Infect Dis. 1997;175:118–22.

    Article  Google Scholar 

  40. Maruszynski M, Pojda Z. Interleukin 6 (IL-6) levels in the monitoring of surgical trauma. A comparison of serum IL-6 concentrations in patients treated by cholecystectomy via laparotomy or laparoscopy. Surg Endosc. 1995;9:882–5.

    CAS  Google Scholar 

  41. Yanagawa H, Sone S, Takahashi Y, Haku T, Yano S, Shinohara T, Ogura T. Serum levels of interleukin 6 in patients with lung cancer. Br J Cancer. 1995;71:1095–8.

    Article  CAS  Google Scholar 

  42. Fiorito S, Magrini L, Goalard C. Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic osteolysis. J Bone Joint Surg Br. 2003;85:1202–6.

    Article  CAS  Google Scholar 

  43. Brodbeck WG, Voskerician G, Ziats NP, Nakayama Y, Matsuda T, Anderson JM. In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry. J Biomed Mater Res A. 2003;64:320–9.

    Article  Google Scholar 

  44. Scaglione S, Cilli M, Fiorini M, Quarto R, Pennesi G. Differences in chemical composition and internal structure influence systemic host response to implants of biomaterials. Int J Artif Organs. 2011;34:422–31.

    Article  Google Scholar 

  45. Caruso R, Trunfio S, Milazzo F, Campolo J, De Maria R, Colombo T, Parolini M, Cannata A, Russo C, Paino R, Frigerio M, Martinelli L, Parodi O. Early expression of pro- and anti-inflammatory cytokines in left ventricular assist device recipients with multiple organ failure syndrome. ASAIO J. 2010;56:313–8.

    CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Kirsten Tornow and Urte Kellner for excellent technical support. This study was supported by the Federal state of Mecklenburg-Vorpommern and the Helmholtz Association of German Research Centres (grant no. VH-MV1) and by the Federal Ministry of Education and Research (grant no. 13N9779, Campus PlasmaMed).

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry and Molecular Biology, Research Group of Predictive Diagnostics, Ernst Moritz Arndt University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany

    Uwe Walschus, Silke Lucke & Michael Schlosser

  2. Institute of Pathophysiology, University of Greifswald, Karlsburg, Germany

    Uwe Walschus & Michael Schlosser

  3. Department of Surgery, University of Greifswald, Greifswald, Germany

    Andreas Hoene & Maciej Patrzyk

  4. Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany

    Birgit Finke, Martin Polak & Karsten Schroeder

  5. Department of Internal Medicine, University of Rostock, Rostock, Germany

    Barbara Nebe

  6. Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, Rostock, Germany

    Andreas Podbielski

  7. Department of Surgery, Hospital Demmin, Demmin, Germany

    Lutz Wilhelm

Authors
  1. Uwe Walschus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Hoene
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maciej Patrzyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Birgit Finke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Polak
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Silke Lucke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Barbara Nebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karsten Schroeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andreas Podbielski
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lutz Wilhelm
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael Schlosser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Schlosser.

Additional information

Uwe Walschus and Andreas Hoene contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walschus, U., Hoene, A., Patrzyk, M. et al. Serum profile of pro- and anti-inflammatory cytokines in rats following implantation of low-temperature plasma-modified titanium plates. J Mater Sci: Mater Med 23, 1299–1307 (2012). https://doi.org/10.1007/s10856-012-4600-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4600-z

Keywords

Search

Navigation