Periodontal diseases, such as chronic periodontitis, share common inflammatory risk factors with other systemic and chronic inflammatory disorders. Mucosal tissues, such as oral epithelia, are exposed to environmental stressors, such as tobacco and oral bacteria, that might be involved in promoting a systemic inflammatory state. Conversely, chronic disorders can also affect oral health. This review will summarize recent evidence for the interrelationship between chronic periodontitis and other prevalent chronic diseases such as cardiovascular diseases, diabetes, cancer and chronic respiratory diseases. The association with pregnancy is also included due to possible obstetric complications. We will focus on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have been shown to be increased in patients with chronic periodontitis, in patients with chronic systemic diseases, and in patients with both chronic periodontitis and other chronic diseases. Therefore, an imbalance towards a proinflammatory immune response could underline a bidirectional link between chronic periodontitis and other chronic diseases. Finally, we highlight that a close coordination between dental and other health professionals could promote oral health and prevent or ameliorate other chronic diseases.

Although a number of inflammatory cytokines have been shown to be associated with periodontal pathogenesis, it is important to investigate further whether these biomarkers are associated with the degree of success in nonsurgical treatment of chronic periodontitis. The aim of the present study was to quantify the total levels of interleukin (IL)-1α, -1β, -6, -10 and tumour necrosis factor (TNF)-α in gingival crevicular fluid (GCF) of chronic periodontitis patients prior to and following nonsurgical periodontal therapy. In total, 52 GCF samples from disease sites of patients with chronic periodontitis, prior to and following periodontal therapy, and ten non-disease sites from non-periodontitis subjects, were collected and cytokine concentrations were determined using a multiplex method. Periodontal parameters, including bleeding on probing, probing pocket depth and the clinical attachment level, in all the sites were recorded. Untreated disease sites exhibited higher cytokine levels in the GCF when compared with the non-disease sites. Nonsurgical periodontal therapy resulted in a statistically significant decrease in the total levels of IL-1α, -1β and -6 in the GCF, but not in IL-10 or TNF-α. The results support the hypothesis that proinflammatory cytokines, including IL-1α, IL-1β and IL-6, are likely to be involved in the pathogenesis of periodontitis and are good markers to evaluate the success of nonsurgical therapy in disease sites of patients with periodontitis.

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Results. It was found that the HFE C282Y mutation occurs in 94.2% of chromosomes from patients with HH. Eighty patients (92.0%) were homozygous for the C282Y mutation and one was heterozygous. Three patients were heterozygous for both C282Y and H63D mutations. One patient was homozygous and one was heterozygous for the H63D mutation. One patient carried normal alleles. In healthy controls, the C282Y mutation occurred in nine subjects (7.7%), all of which were heterozygous. The H63D mutation was found in 28 control subjects, one of which was homozygous. Conclusions. We found that the majority of patients with HH have the C282Y mutation in the HFE gene. The frequency of the H63D mutation was higher in controls than in patients with HH, although in chromosomes at risk the frequency of the H63D mutation was higher in patients.

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Iron accumulation in the liver in hereditary hemochromatosis (HH) has been shown to be highly variable. Some studies point to the importance of major histocompatibility complex (MHC) class I (MHC-I) and CD8 ؉ cells as modifiers of iron overload. In this report, using mice knockout for H2K b؊/؊ and H2D b؊/؊ genes, it is demonstrated that lack of classical MHC-I molecules results in a spontaneous increase of nonheme iron content in the liver (mainly located in the hepatocytes) when compared to wild-type mice. In CD8 ؊/؊ and Rag2 ؊/؊ mice, no spontaneous hepatic iron accumulation was ob- IntroductionSince the discovery of the HFE gene, 1 several molecules implicated in heritable defects of iron metabolism have been identified, giving new insights into the molecular control of cellular pathways of iron balance. 2 Despite these advances, a considerable unexplained variability in the amount of iron loading in HFE hemochromatosis still persists. 3,4 Thus, the finding of new molecular regulators to further improve our understanding of iron homeodynamics continues to be pertinent. Recently, Andrews and collaborators made an important contribution in this area by characterizing genes that modify the hemochromatosis phenotype in mice. They reported that mice double knockout for Hfe and ␤ 2 -microglobulin (␤ 2 m) accumulate more tissue iron than mice lacking Hfe only. 4 This finding suggests that other(s) ␤ 2 m-interacting protein(s), such as classical major histocompatibility complex (MHC) class I molecule(s) (MHC-I), may be involved in iron regulation. Alternatively, MHC-dependent cells such as CD8 ϩ T lymphocytes or others could play a role in iron metabolism. 5 To further explore other candidate molecular and cellular regulators of iron balance, we investigated the spontaneous iron status of mice with disrupted classical Mhc-I genes and of mice knockout for CD8 and Rag2 genes. Study designC57BL/6J (B6), H2K bϪ/Ϫ , H2D bϪ/Ϫ single-knockout and H2K bϪ/Ϫ D bϪ/Ϫ double-knockout mice were raised at the Pasteur Institute animal facilities and are reported elsewhere. 6 All H2 knockout mice were backcrossed onto the B6 background for 12 generations. The CD8 knockout mice (CD8␣ Ϫ/Ϫ ) 7 that had been backcrossed to B6 for 13 generations were purchased from The Jackson Laboratory (Bar Harbor, ME) at 8 to 9 weeks and aged at the Institute for Molecular and Cell Biology (IBMC) animal facility. Rag2 Ϫ/Ϫ8 were backcrossed 9 times onto the B6 background; additional B6 mice were bred in IBMC. All mice used in this study were male, aged 4 to 5 months, and were maintained on standard mouse diet. Iron status was evaluated as previously described. 9 Iron staining in the liver was performed by using the Perls Prussian blue method, and evaluation of ferritin accumulation was done by electron microscopy in liver samples processed as described. 10 The blood samples were obtained by cardiac puncture in mice under anesthesia or by retro-orbital bleeding. Serum transferrin saturation was calculated by dividing serum iron by total iron-binding cap...

Human intrahepatic lymphocytes are enriched in CD1d-unrestricted T cells coexpressing NKR. Although the origin of this population remains controversial, it is possible to speculate that the hepatic microenvironment, namely epithelial cells or the cytokine milieu, may play a role in its shaping. IL-15 is constitutively expressed in the liver and has a key role in activation and survival of innate and tissue-associated immune cells. In this in vitro study, we examined whether hepatocyte cell lines and/or IL-15 could play a role in the generation of NK-like T cells. The results show that both HepG2 cells and a human immortalized hepatocyte cell line increase survival and drive basal proliferation of T cells. In addition, IL-15 was capable of inducing Ag-independent up-regulation of NKR, including NKG2A, Ig-like receptors, and de novo expression of CD56 and NKp46 in CD8+CD56− T cells. In conclusion, our study suggests that hepatocytes and IL-15 create a favorable microenvironment for T cells to growth and survive. It can be proposed that the increased percentage of intrahepatic nonclassical NKT cells could be in part due to a local CD8+ T cell differentiation.

Understanding the rationale for the generation of a pool of highly differentiated effector memory CD8+ T cells displaying a weakened capacity to scrutinize for peptides complexed with major histocompatibility class I molecules via their T cell receptor, lacking the “signal 2” CD28 receptor, and yet expressing a highly diverse array of innate receptors, from natural killer receptors, interleukin receptors, and damage-associated molecular pattern receptors, among others, is one of the most challenging issues in contemporary human immunology. The prevalence of these differentiated CD8+ T cells, also known as CD8+CD28−, CD8+KIR+, NK-like CD8+ T cells, or innate CD8+ T cells, in non-lymphoid organs and tissues, in peripheral blood of healthy elderly, namely centenarians, but also in stressful and chronic inflammatory conditions suggests that they are not merely end-of-the-line dysfunctional cells. These experienced CD8+ T cells are highly diverse and capable of sensing a variety of TCR-independent signals, which enables them to respond and fine-tune tissue homeostasis.