Plasma cytokine profiles following subcutaneous implantation of titanium in mice
Takashi Oda, Hodaka Sasaki, Taichi Ito, Hideshi Sekine, Tetsuo Kato, Masao Yoshinari, Yasutomo Yajima
Department of Oral and Maxillo-Facial Implantology, Tokyo Dental College, Chiba, Japan Division of Oral Implants Research and HRC7, Oral Health Science Center, Tokyo Dental College, Chiba, Japan.
Division of Oral Implants Research and HRC7, Oral Health Science Center, Tokyo Dental College, Chiba, Japan.
Division of Oral Implants Research and HRC7, Oral Health Science Center, Tokyo Dental College, Chiba, Japan Department of Oral and Maxillo-Facial Implantology, Tokyo Dental College, Tokyo, Japan.
Division of Oral Implants Research and HRC7, Oral Health Science Center, Tokyo Dental College, Chiba, Japan Laboratory of Chemistry, Tokyo Dental College, Tokyo, Japan.
DOI: 10.4236/jbise.2013.69113   PDF    HTML   XML   3,257 Downloads   5,018 Views   Citations


Aims and Objectives: The purpose of this study was to investigate the influence of a titanium implant on immune response in mouse by monitoring change in plasma cytokine profiles. Materials and Methods: C57BL/6 (type 1 T helper cell-predominant) and BALB/c (type 2 T helper cell-predominant) mice were used. Each type was divided into an experimental and a control group: in the former, pure titanium implants (Φ 1 mm × 1 mm) were inserted into the back of the mice subcutaneously; in the latter, the wound was sutured closed with no insertion of an implant. Blood samples were collected before implantation and at 3 hr, 24 hr, 3 d, 1 mo, and 3 mo after implantation. Levels of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17A, IL-23, IFN-γ, TNF-α, and TGF-β1 were measured by multi-analyte enzyme-linked immunosorbent assay. Results: Baseline cytokine levels were generally higher in the BALB/c mice than in their C57BL/6 counterparts. Cytokine levels showed only slight variation after implantation of titanium in ei-ther strain. No statistically significant differences in cytokine levels were detected, except for those of IL-6 and IL-10. Conclusion: The results showed that titanium implantation induced no clear Th1-, Th2-, or Th17-mediated immune response in either Th1-or Th2-predominant mice.

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Oda, T. , Sasaki, H. , Ito, T. , Sekine, H. , Kato, T. , Yoshinari, M. and Yajima, Y. (2013) Plasma cytokine profiles following subcutaneous implantation of titanium in mice. Journal of Biomedical Science and Engineering, 6, 928-933. doi: 10.4236/jbise.2013.69113.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Pohler, O.E. (2000) Unalloyed titanium for implants in bone surgery. Injury, 31, 7-13. doi:10.1016/S0020-1383(00)80016-9
[2] Schmidt, B.L., Perrott, D.H., Mahan, D., et al. (1998) The removal of plates and screws after Le Fort I osteotomy. Journal of Oral and Maxillofacial Surgery, 56, 184-188. doi:10.1016/S0278-2391(98)90865-5
[3] Leonard, J.P., Waldburger, K.E. and Goldman, S.J. (1995) Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. The Journal of Experimental Medicine, 181, 381-386. doi:10.1084/jem.181.1.381
[4] Durham, S.R. and Till, S.J. (1998) Immunologic changes associated with allergen immunotherapy. Journal of Allergy and Clinical Immunology, 102, 157-164. doi:10.1016/S0091-6749(98)70079-X
[5] Clerici, M. and Shearer, G.M. (1993) A TH1→TH2 switch is a critical step in the etiology of HIV infection. Immunology Today, 14, 107-111. doi:10.1016/0167-5699(93)90208-3
[6] Liskmann, S., Vihalemm, T., Salum, O., et al. (2006) Correlations between clinical parameters and interleukin-6 and interleukin-10 levels in saliva from totally edentulous patients with peri-implant disease. The International Journal of Oral & Maxillofacial Implants, 21, 543-550.
[7] Duarte, P.M., de Mendonca, A.C., Máximo, M.B., et al. (2009) Effect of anti-infective mechanical therapy on clinical parameters and cytokine levels in human peri-implant diseases. Journal of Periodontology, 80, 234-243. doi:10.1902/jop.2009.070672
[8] Birkedal-Hansen, H. (1993) Role of cytokines and inflammatory mediators in tissue destruction. Journal of Periodontal Research, 28, 500-510. doi:10.1111/j.1600-0765.1993.tb02113.x
[9] Genco, R.J. (1992) Host responses in periodontal diseases: Current concepts. Journal of Periodontology, 63, 338-355. doi:10.1902/jop.1992.63.4s.338
[10] Schierano, G., Bassi, F., Gassino, G., et al. (2000) Cytokine production and bone remodeling in patients wearing overdentures on oral implants. Journal of Dental Research, 79, 1675-1682. doi:10.1177/00220345000790090701
[11] Javed, F., Al-Hezaimi, K., Salameh, Z., et al. (2011) Proinflammatory cytokines in the crevicular fluid of patients with peri-implantitis. Cytokine, 53, 8-12. doi:10.1016/j.cyto.2010.08.013
[12] Candel-Martí, ME., Flichy-Fernández, AJ., Alegre-Domingo, T., et al. (2011) Interleukins IL-6, IL-8, IL-10, IL-12 and periimplant disease. Medicina Oral, Patología Oral y Cirugía Bucal, 16, 518-521. doi:10.4317/medoral.16.e518
[13] Scott, P. (1991) IFN-γ modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. The Journal of Immunology, 147, 3149-3155.
[14] Chensue, S.W., Ruth, J.H., Warmington, K., et al. (1995) In vivo regulation of macrophage 11-12 production during type 1 and type 2 cytokine-mediated granuloma formation. The Journal of Immunology, 155, 3546-3551.
[15] Haraguchi, S., Good, R.A., James-Yarish, M., et al. (1995) Differential modulation of Th1-and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein. Proceedings of the National Academy of Sciences, 92, 3611-3615. doi:10.1073/pnas.92.8.3611
[16] Tallima, H., Salah, M., Guirguis, FR., et al. (2009) Transforming growth factor-b and Th17 responses in resistance to primary murine schistosomiasis mansoni. Cytokine, 48, 239-245. doi:10.1016/j.cyto.2009.07.581
[17] Lalor, P.A., Revell, P.A., Gray, A.B., et al. (1991) Sensitivity to titanium, a cause of implant failure? The Bone & Joint Journal, 73, 25-28.
[18] Hunt, J.A., Williams, D.F., Ungersbock, A., et al. (1994) The effect of titanium debris on soft tissue response. Journal of Materials Science: Materials in Medicine, 5, 381-383. doi:10.1007/BF00058968
[19] Katou, F., Andoh, N., Motegi, K., et al. (1996) Immunoinflammatory responses in the tissue adjacent to titanium miniplates used in the treatment of mandibular fractures. Journal of Cranio-Maxillofacial Surgery, 24, 155-162. doi:10.1016/S1010-5182(96)80049-7
[20] Smith, D., Lugowski, S., McHugh, A., et al. (1997) Systemic metal ion levels in dental implant patients. The International Journal of Oral & Maxillofacial Implants, 12, 828-834.
[21] Prete, G.D., Carli, M.D., Almerigogna, F., et al. (1993) Human IL10 is produced by both type 1 helper (Thl) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. The Journal of Immunology, 150, 353.
[22] Groux, H., O’Garra, A., Bigler, M., et al. (1997) ACD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature, 389, 737-742. doi:10.1038/39614
[23] Opal, S.M. and DePalo, V.A. (2000) Anti-inflammatory cytokines. Chest, 117, 1162-1172. doi:10.1378/chest.117.4.1162
[24] Afzali, B., Lombardi, G., Lechler, RI., et al. (2007) The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clinical & Experimental Immunology, 148, 32-46. doi:10.1111/j.1365-2249.2007.03356.x
[25] Yamashita, K., Sakai, M., Takemoto, N., et al. (2009) Attenuation of delayed-type hypersensitivity by fullerene treatment. Toxicology, 261, 19-24. doi:10.1016/j.tox.2009.04.034
[26] Leopold, S.S., Berger, R.A., Patterson, L., et al. (2000) Serum Titanium level for diagnosis of a failed, metalbacked patellar component. The Journal of Arthroplasty, 15, 938-943. doi:10.1054/arth.2000.6632
[27] Wappelhorst, O., Kühn, I., Heidenreich, H., et al. (2002) Transfer of selected elements from food into human milk. Nutrition, 18, 316-322. doi:10.1016/S0899-9007(01)00798-5

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