Periodontitis Impact in Interleukin-6 Serum Levels in Solid Organ Transplanted Patients: A Systematic Review and Meta-Analysis

Abstract

This systematic review aimed to investigate the influence of periodontitis on post-transplant IL-6 serum levels of solid organ transplanted patients as compared to healthy subjects. Four databases (PubMed, Scholar, EMBASE, and CENTRAL) were searched up to February 2020 (PROSPERO CRD42018107817). Case-control and cohort studies on the association of IL-6 serum levels with a periodontal status of patients after solid organ transplantation were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses were thoroughly conducted. GRADE assessment provided quality evidence. Four case-control studies fulfilled the inclusion criteria (274 transplant recipients and 146 healthy controls), all of low risk of bias. Meta-analyses revealed significantly higher IL-6 levels in transplanted patients than healthy individuals with low-quality evidence (Mean Difference (MD): 2.55 (95% confidence interval (CI): 2.07, 3.03)). Transplanted patients with periodontitis have higher serum IL-6 levels than transplanted patients without periodontitis with moderate quality evidence (MD: 2.20 (95% CI: 1.00, 3.39)). We found low-quality evidence of higher IL-6 levels than healthy patients in patients with heart and kidney transplant. In these transplanted patients, there was moderate quality evidence that periodontitis is associated with higher IL-6 serum levels. Future research should consider the impact of such a difference in organ failure and systemic complications.

Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption

“…Furthermore, IL-6-neutralizing antibodies inhibit TNF-α and IL-1β-stimulated osteoclast formation [119]. Therefore, it is recognized that IL-6 is a promoter of osteoclastic bone resorption and centrally involved in the pathogenesis of bone loss in chronic and acute inflammation [118], periodontitis [120], rheumatoid arthritis, and osteoporosis [121]. It has been reported that treatment with exogenous proinflammatory cytokines, such as IL-1β and TNF-α, as well as combinations of IL-1β, TNF-α, and IL-6, upregulates IL-6 expression in a human osteocyte-rich cell fraction [28].…”

Association between Periodontitis and High Blood Pressure: Results from the Study of Periodontal Health in Almada-Seixal (SoPHiAS)

“…The oral sequelae of the disease, that if untreated ultimately leads to tooth loss, increases morbidity, reduces quality of life and work productivity [13]. Current evidence suggests periodontitis as a risk factor for CVDs, metabolic conditions, chronic respiratory and neurological disorders, rheumatoid arthritis, immunity conditions, stress or cancer [14][15][16][17][18][19][20][21]. Similarly, epidemiological and limited interventional studies worldwide have observed an association between periodontitis and hypertension [18,22].…”

Dental Implant Failure Rate and Marginal Bone Loss in Transplanted Patients: A Systematic Review and Meta-Analysis

“…Thus, future studies should employ up-to-date case definitions [42], as well as more detailed clinical data. However, the shortage in available studies precluded additional tests in biological surrogates comparison, for instance cytokines, as they were previously reported as increased in SOT patients [16] and publication bias inspection.…”

“…According to GODT, in 2017, more than 139 thousand organ transplants were performed, corresponding to 16 organ transplants per hour. To prevent organ rejection, these patients undergo a chronic regimen of immunosuppressants, which puts them at higher risk of infections and inflammation [13][14][15][16]. In patients taking these medications, there is evidence that wound healing and bone metabolism may be impaired, due to either inhibition of osteoblast function and osteogenesis or to a concomitant increase of bone resorption and osteoporosis, which may result in decreased bone-to-implant contact [17][18][19][20].…”