Abstract
Hypersensitivity reactions to titanium (Ti) are very rare. Thus, we assessed the proinflammatory response and also potential tolerance favoring in vitro reactivity of human blood lymphocytes and monocytes (PBMC) to Ti in healthy individuals (14 without, 6 with complication-free dental Ti implants). The proliferation index (SI) in lymphocyte transformation test (LTT) and production of cytokines linked to innate immune response (IL-1β, IL-6, and TNFα) or immune regulation (IL-10) were assessed in response to TiO2 particles or Ti discs. In both groups, the Ti-LTT reactivity was not enhanced (e.g., SI < 3). The control antigen tetanus toxoid (TT) gave adequate reactivity (median SI individuals without/with implant: 20.6 ± 5.97/19.58 ± 2.99). Individuals without implant showed higher cytokine response to Ti materials than individuals with symptom-free implants; for example, TiO2 rutile particle induced increase of IL-1β 70.27-fold/8.49-fold versus control medium culture. PBMC of 5 of the 6 individuals with complication-free Ti implants showed an ex vivo ongoing production of IL-10 (mean 4.18 ± 2.98 pg/mL)-but none of the 14 controls showed such IL-10 production. Thus in vitro IL-1β-, IL-6-, and TNF-α production reflects “normal” unspecific immune response to Ti. This might be reduced by production of tolerogenic IL-10 in individuals with symptom-free Ti dental implants.
Highlights
Cutaneous hyperreactivity to metals is common with nickel (Ni) and to a lesser extent cobalt (Co) and chromium (Cr) being typical elicitors
The role of Ti in the induction of a IL-1-related periimplant inflammation with subsequent bone resorption has been shown in animal models using intramedullary Ti rod implantation and Ti particles introduced onto the calvarium [20, 34]
In the present study, a significant increase of stimulation index (SI) response to TiO2 particles or Ti-discs was not observed. This is in accordance with experiments of Park et al showing that, in the local lymph node assay the SI value did not increase to TiO2 particles, but to eugenol as positive control [41]
Summary
Cutaneous hyperreactivity to metals is common with nickel (Ni) and to a lesser extent cobalt (Co) and chromium (Cr) being typical elicitors. Only very few case reports or small case series exist describing potential hypersensitivity reactions to Ti, for example, axillary dermatitis to a Ti lactate containing antitranspirant; local eczema or inflammatory granulomatous reactions to Ti-based pacemakers; impaired wound/fracture healing upon osteosynthesis; and loosening of hip arthroplasty in association with peri-implant Ti wear particles and patients showing skin test reactivity to a Ti containing ointment [2,3,4,5,6]. Patients prior to implantation or already having Ti-based implants may be concerned by reports on the risk of local or systemic adverse health effects. Some authors have reported high frequency of “hyperreactors” against Ti using lymphocyte transformation test (LTT) [7]. There is a controversial discussion regarding Ti related immune reactivity [8, 9] since the LTT
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