title: Inhibition of T and B cell proliferation by titanium, cobalt, and chromium: role of IL-2 and IL-6.
abstract: The mechanism by which an increased risk of prosthetic infection is induced in patients with total joint arthroplasties is poorly understood. The adverse effects of metallic corrosion products of a prosthesis on host defense mechanisms, particularly immune response and release of immunoregulatory cytokines, remain largely unknown. Titanium, cobalt, and chromium are the materials most often used for joint implantation. Therefore, this study was aimed at investigating the cytotoxicity of titanium, cobalt, and chromium and whether these metals affect T and B cell proliferation and the release of cytokines by human peripheral blood mononuclear cells (PBMC) in vitro. Metal cytotoxicity was not observed judging by cell viability and cell injury after PBMC was extensively exposed to the metals. Phytohemagglutinin (PHA)-induced T cell proliferation and lipopolysaccharide-induced B cell proliferation were significantly inhibited by titanium, chromium, and cobalt. The release of IL-2 and IL-6 by PHA-stimulated PBMC was significantly inhibited by titanium, chromium, and cobalt. Titanium did not alter IFN-gamma production, whereas chromium and cobalt significantly reduced IFN-gamma release by PHA-stimulated PBMC. The addition of IL-2 and IL-6 significantly restored the metal-induced inhibition of T cell and B cell proliferation, respectively. This study sheds light on how the metals impair immune response and cytokine release, suggesting that patients with an extensive exposure to the metals may develop immune dysfunctions. The compromised immune response induced by the metals might significantly contribute to an increased risk of infection in patients with joint prostheses.
authors.affiliation: Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55415, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: D T
authors.initials: DT
authors.lastname: Tsukayama
authors.forename: B H
authors.initials: BH
authors.lastname: Wicklund
authors.forename: R B
authors.initials: RB
authors.lastname: Gustilo
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002857:Chromium / Q000494:pharmacology* / Q000633:toxicity; D003035:Cobalt / Q000494:pharmacology* / Q000633:toxicity; D004198:Disease Susceptibility; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D007376:Interleukin-2 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D013530:Surgical Wound Infection / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014025:Titanium / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015850:Interleukin-6; D010835:Phytohemagglutinins; D002857:Chromium; D003035:Cobalt; D014025:Titanium