Allergy or Tolerance: Reduced Inflammatory Cytokine Response and Concomitant IL-10 Production of Lymphocytes and Monocytes in Symptom-Free Titanium Dental Implant Patients

Hypersensitivity reactions to titanium (Ti) are very rare. Thus, we assessed the proinflammatory response and also potential tolerance favoringin vitroreactivity 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 TiO2particles 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, TiO2rutile particle induced increase of IL-1β70.27-fold/8.49-fold versus control medium culture. PBMC of 5 of the 6 individuals with complication-free Ti implants showed anex vivoongoing production of IL-10 (mean4.18±2.98 pg/mL)-but none of the 14 controls showed such IL-10 production. Thusin vitroIL-1β-, IL-6-, and TNF-αproduction 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.