The first cases of peri-implantitis were described as "inflammatory reactions with loss of supporting bone in the tissues surrounding a functioning implant"31. Later, it was demonstrated that this pathology was physiopathologically different to periodontitis32; and it is currently considered as an inflammatory disorder ("Peri-implant Conditions and Diseases")33.
Inflammation is a physiological response that participates in many acute and chronic diseases in humans34. The term interleukin-1 was firstly used in the International Lymphokine Workshop in Ermatingen in 197935, to define "a macrophagic product that stimulates T and B cells, with non-immunological properties"17. It was later discovered that genetic variations of this cytokine are relevant for the pathogenesis of many inflammatory and malignant disorders (pancreatitis, lupus erythematosus, etc.)36–37. Because there is strong evidence of the role of IL-1β in the physiopathology of periodontitis14, recent research is trying to unveil its link to peri-implantitis.
After conducting a systematic review, we found that only two authors (Egypt and the Netherlands) demonstrated a significant association between the composite genotype of IL-1β (+ 3945) and IL-1α (-889) and the presence of peri-implantitis15,29. This genotype has already been associated to patients with chronic periodontitis, but not with aggressive periodontitis14. We believe that there may be a specific group of patients with peri-implantitis who present this genotypic profile.
Myeloid differentiation factor-88 (MyD88) is responsible for the activation of pro-inflammatory cytokines IL1β and IL-1α, inducing an intracellular cascade system that secretes both proteins to the extracellular matrix38. Unlike IL-1β, IL-1α also has a silent nuclear expression under normal homeostasis, that changes under pathological conditions to initiate the inflammatory response39. Thus, in the recent years it has been postulated that IL-1α would be a dual-function cytokine39. This may explain why IL-1α polymorphism, located at position 889 [IL-1α (-899)], is not independently and significantly associated with the development of PI15,16,26−29.
During the eligibility analysis, several studies were excluded because they did not indicate the diagnostic criteria of PI. Interestingly, Feloutzis et al.40 and Gruica et al.41 found a significant association between SNP IL-1β (+ 3953) and peri-implant bone loss, only in heavy smokers (> 20 cigarettes/day). However, they did not indicate whether the patients had peri-implantitis42–43. Furthermore, our analysis didn’t find a significant association between IL-1β (+ 3953) polymorphism, tobacco use and of PI15,16,26,28.
In contrast, two study groups from Japan did report the link between IL-1β (-511) and PI26,28. After performing the meta-analysis with the rest of the studies, this relationship remain statistically significant. We believe this positive result is because the authors used ABL > 0.5 mm as diagnostic criteria for PI26,28. Although the first sign of peri-implantitis can be the presence of a bone loss (0.5 mm)44, diagnosis of PI is based on: 1) presence of bleeding and/or suppuration on gentle probing, 2) probing depths of ≥ 6 mm, or bigger than previous examinations, and 3) bone levels ≥ 3 mm apical of the most coronal portion of the intraosseous part of the implant, or greater than initial bone remodelling33. Therefore, dental implants with diagnosis of peri-implantitis in some studies15,26,28, could currently be reclassified as peri-implant health.
In addition, the diagnostic criteria of peri-implanitis have been in constant change thought the years32,45, and it is not possible to ensure that all the patients were correctly classified as either healthy or sick, with respect to PI. Since these variations are very important in risk assessment studies, the application of the latest classification of periodontal diseases may reduce this bias, allowing the homogeneity of future investigations46.