title: Prosthetic metals impair murine immune response and cytokine release in vivo and in vitro.
abstract: This study was designed to investigate whether prosthetic metals adversely affect immune responses and the release of immunoregulatory cytokines in vivo and in vitro. Titanium and cobalt-chromium alloy were injected into the peritoneal cavity of female mice. At 5, 8, and 12 weeks after the injection, the levels of cobalt and chromium in the blood were significantly increased compared with the levels in control mice; the level of titanium was not significantly changed until 12 weeks. The release of interleukin-2 was significantly inhibited by cobalt-chromium particles after 3 weeks; titanium particles did not have the same effect until 8 and 12 weeks. The release of interleukin-4 was significantly inhibited by cobalt-chromium particles after 3 weeks but was not significantly inhibited by titanium particles until 12 weeks. The release of interferon-gamma was significantly inhibited by cobalt-chromium particles only at 12 weeks and was not inhibited by titanium particles. The proliferation of T cells was significantly inhibited by cobalt-chromium particles at 3 weeks and by titanium particles at 8 and 12 weeks, and the proliferation of B cells was significantly inhibited by cobalt-chromium particles after 3 weeks but was not inhibited by titanium particles. The production of immunoglobulin by lipopolysaccharide-stimulated B cells was also significantly reduced by cobalt-chromium particles after 3 weeks and by titanium particles at 8 and 12 weeks. The cytokine release by lymphocytes, proliferation of T and B cells, and immunoglobulin production by B cells were also significantly inhibited by titanium and cobalt-chromium particles, as well as by titanium, cobalt, and chromium ions in vitro, whereas these metals are not cytotoxic to murine lymphocytes in vitro. The data indicate that the metal-induced immunosuppression may be another important factor in the development of implant-associated infection in patients with a prosthesis.
authors.affiliation: Musculoskeletal Sepsis Unit, Hennepin County Medical Center, Minneapolis, Minnesota 55455, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: B H
authors.initials: BH
authors.lastname: Wicklund
authors.forename: R B
authors.initials: RB
authors.lastname: Gustilo
authors.forename: D T
authors.initials: DT
authors.lastname: Tsukayama
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002857:Chromium / Q000097:blood; D002858:Chromium Alloys / Q000494:pharmacology*; D003035:Cobalt / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007109:Immunity / Q000187:drug effects; D007136:Immunoglobulins / Q000378:metabolism; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019736:Prostheses and Implants; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014025:Titanium / Q000097:blood / Q000494:pharmacology*
chemical_list: D002858:Chromium Alloys; D016207:Cytokines; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D002857:Chromium; D003035:Cobalt; D014025:Titanium