The role of IL‐6 on apical periodontitis: a systematic review

The aim of this review was to examine current knowledge of the role of interleukin‐6 (IL‐6) in apical periodontitis (AP) pathogenesis as an inflammatory or pro‐inflammatory cytokine. It also looked at whether IL‐6 could serve as a measure for differential diagnosis or as a biomarker that can further predict the progression of bone resorption. A systematic review relating to AP and IL‐6 was made via PubMed, BIOSIS, Cochrane, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts. The reference lists of the identified publications were examined for additional titles. Eighteen papers were studied in total. In vitro studies (n = 6) revealed that IL‐6 is present in AP, and its levels are proportional to the size of the periapical lesions. Neutrophils and macrophages resident in these lesions can produce IL‐6 in vitro after a bacterial stimulus. Animal studies (n = 5) showed that IL‐6 is present in AP and that osteoblasts can produce IL‐6 in vivo. On the other hand, two studies using IL‐6 knockout mice revealed larger periapical lesions when compared with control groups, demonstrating IL‐6's role as an anti‐inflammatory cytokine. In human studies (n = 7), IL‐6 was identified in AP, and its levels were higher in symptomatic, epithelialized and large lesions than in asymptomatic and small lesions. These data lead to the conclusion that IL‐6 may play a pro‐inflammatory role, increasing its levels and reabsorbing bone in the presence of infections. When IL‐6 is not present, other cytokines such as IL‐1 and TNF‐α induce bone resorption. Further studies about the relationship between AP development and the cytokine network must be performed to establish the exact role of each cytokine in the inflammatory process.     

Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.     

Anti-ageing effects of dentifrices containing anti-oxidative,anti-inflammatory,and anti-bacterial agents (Tomarina) on gingival collagen degradation in rats

Objective

Previous studies have demonstrated the relationship between ageing and oxidative stress. In this study, we examined the effects of topical application of a dentifrice containing anti-oxidative, anti-inflammatory, and anti-bacterial agents (Tomarina^®) to the gingival surface on gingival collagen degradation in rats.

Design

Fischer 344 male rats (4 or 8 months old) were divided into two groups: experimental group and control group. Tomarina^® (the experimental group) or control dentifrice (the control group) was applied 5 days per week for 2 months.

Results

In the control group, gingival collagen density decreased with ageing. In the experimental group, the collagen density did not change with ageing, and was greater than that in the control group at 10 months of age (p < 0.0083). In addition, the control group showed an increase in serum oxidative stress with ageing. The experimental group also showed increased serum oxidative stress, but the value was lower than the control group at 10 months of age (p < 0.0083). Furthermore, low expressions of protein oxidative damage in the periodontal tissue were observed in the experimental group, compared to the control group at 6 months and 10 months.

Conclusion

These findings indicate that Tomarina^® might suppress the effects of ageing on gingival collagen degradation, by decreasing oxidative stress in the rat model.     

Peptide vaccination for patients with melanoma and other types of cancer based on pre-existing peptide-specific ctotoxic T-lymphocyte precursors in the periphery

Identification of antigenic peptides expressed on cancer cells enables us to treat cancer patients with peptide-based immunotherapy. Although optimal protocols for peptide-based vaccines have not yet been elucidated, boosting the immune system could be a better approach than priming the immune system to elicit prompt and potent peptide-specific T-cell responses in cancer patients. With this possibility in mind, the authors undertook a clinical trial in which cancer patients were vaccinated with peptides (maximum 4) after confirmation of pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the periphery. Fourteen patients (seven with melanoma and seven with other types of cancer) positive for either HLA-A24 or HLA-A2 were enrolled in this study. Fourteen and 16 peptides were used to screen for HLA-A24+ and HLA-A2+ patients, respectively. The vaccination was well tolerated, and the only adverse effects were local pain and fever. Kinetic analysis revealed that peptide-reactive CTLs increased after peptide vaccination in 7 of 14 patients. Immunoglobulin G (IgG) reactive to the administered peptides was detected in 2 patients before vaccination, although it became detectable in 8 of the other 12 patients after the peptide vaccination. Stable disease for more than 6 months was observed in five patients (one with melanoma and four with other types of cancer); all of these patients showed increased levels of peptide-specific IgG. These results indicate that peptide vaccination of patients showing evidence of pre-existing peptide-specific CTL precursors can be applied in further clinical trials aimed at the treatment of melanoma and other types of cancer.