Orthopaedic implant related metal toxicity in terms of human lymphocyte reactivity to metal-protein complexes produced from cobalt-base and titanium-base implant alloy degradation

Metal toxicity from sources such as orthopaedic implants was investigated i n terms of immune system hyper-reactivity to metal implant alloy degradatio n products. Lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in this in vitro study using pri mary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium mo lybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium alloy (Ti-6Al-4V, ASTM F- 136) beads (70 mum) were incubated in agitated human serum at 37 degrees Ce lsius to simulate naturally occurring metal implant alloy degradation proce sses. Particulate free serum samples, which were incubated with metal, were then separated into molecular weight based fractions. The amounts of solub le Cr and Ti within each serum fraction were measured and correlated with l ymphocyte proliferation response to the individual serum fractions. Lymphoc ytes from each subject were cultured with 11 autologous molecular weight ba sed serum fractions either with or without added metal. Two molecular weigh t ranges of human serum proteins were associated with the binding of Cr and Ti from Co-Cr-Mo and Ti implant alloy degradation (at < 30 and 180-330 kDa ). High molecular weight serum proteins (approximate to 180 kDa) demonstrat ed greater lymphocyte reactivity when complexed with metal released from Co -Cr-Mo alloy and Ti alloy than with low (5-30 kDa) and midrange (30-77 kDa) serum proteins. When the amount of lymphocyte stimulation was normalized t o both the moles of metal and the moles of protein within each fraction (Me tal-Protein Complex Reactivity Index, MPCRI), Cr from Co-Cr-Mo alloy degrad ation demonstrated approximately 10 fold greater reactivity than Ti in the higher molecular weight serum proteins (approximate to 180-250 kDa). This i n vitro study demonstrated a lymphocyte proliferative response to both Co-C r-Mo and Ti alloy metalloprotein degradation products. This response was gr eatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.