Cytokines and chemokines associated with Treg/Th17 response in chronic inflammatory periapical disease

Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.

Treg and Th17 cells in inflammatory periapical disease: a systematic review

Abstract: The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T helper 17 cell (Th17) responses. The objective of this study was to conduct a frequency systematic review to determine the presence of Treg/Th17 responses and the influence of these cells in the progression of chronic inflammatory periapical lesions in humans. A systematic computerized search was carried out in Pubmed, Medline, Web of Science and Scopus electronic databases from their date of inception through the first week of May 2017. In addition, the reference lists of the included articles and the grey literature were hand-searched. Articles that evaluated the presence and influence of Treg/Th17 in the progression of human periapical lesions were included. Study selection and the quality assessment of the included articles (using the Newcastle-Ottawa scale) were carried out by two authors. Fifty-seven titles/abstracts were screened and eight studies met the eligibility criteria and were included in this systematic review. The included studies showed large variation in the type of periapical lesion assessed, mean age, age range, type of experiment and findings regarding the participation of Th17 and Treg in the status of inflammatory periapical lesions. The studies showed the involvement of Treg in the modulation of the inflammatory response in radicular cysts and periapical granulomas. This systematic review highlights the relationship between Treg and Th17 acting in a subtle balance inhibiting or promoting the progression of human periapical lesions.

The recurrence of leprosy reactional episodes could be associated with oral chronic infections and expression of serum IL-1, TNF-á, IL-6, IFN-ã and IL-10

The aim of this study was to determine whether the presence of leprosy reactional episodes could be associated with chronic oral infection. Thirty-eight leprosy patients were selected and divided into 2 groups: group I - 19 leprosy patients with oral infections, and group II - 19 leprosy patients without oral infections. Ten patients without leprosy, but presenting oral infections, were assigned to the control group. Leprosy patients were classified according to Ridley and Jopling classification and reactional episodes of the erythema nodosum type or reversal reaction were identified by clinical and histopathological features associated with serum IL-1, TNF-?, IL-6, IFN-? and IL-10 levels. These analyses were performed immediately before and 7 days after the oral infection elimination. Patients from group I presenting oral infections reported clinical improvement of the symptoms of reactional episodes after dental treatment. Serum IL-1, TNF-?, IL-6, IFN-? and IL-10 levels did not differ significantly before and after dental treatment as determined by the Wilcoxon test (p>0.05). Comparison of the 2 groups showed statistically significant differences in IL-1 and IL-6 at baseline and in IL-1, IL-6 and IL-10 on the occasion of both collections 7 days after therapy. Serum IL-6 and IL-10 levels in group I differed significantly at baseline compared to control (Mann-Whitney test; p<0.05). These results suggest that oral infection could be involved as a maintenance factor in the pathogenesis of leprosy reactional episodes.

O objetivo deste estudo foi determinar se os episódios reacionais da hanseníase podem estar associados a infecções orais crônicas. Trinta e oito pacientes com hanseníase foram selecionados e divididos em dois grupos: grupo I & 19 pacientes com hanseníase apresentando infecções orais, e grupo II & 19 pacientes com hanseníase sem infecções orais. Os pacientes foram classificados, quanto à forma clínica da doença, de acordo com Ridley and Jopling, e os episódios reacionais, tipo eritema nodoso e reação reversa, foram identificados pelas características clínicas, histopatológicas associadas à quantificação no soro de IL-1, TNF-?, IL-6, IFN-? e IL-10. Estas analises foram realizadas imediatamente antes e 7 dias após a resolução dos focos de infecção. Pacientes do grupo I aprentando infecções orais relataram melhora clínica dos sintomas dos episódios reacionais após o tratamento odontológico. Os níveis séricos de IL-1, TNF-?, IL-6, IFN-? e IL-10 não diferiram significantemente antes e após o tratamento odontológico, como determinado pelo teste Wilcoxon (p>0,05). As comparações entre os grupos mostrou diferenças estatisticamente significantes nos níveis de IL-1 e IL-6 na coleta inicial e nos níveis de IL-1, IL-6 e IL-10 nas duas coletas 7 dias após o tratamento (teste Mann-Whitney; p<0,05). Estes resultados sugerem que infecções orais estão envolvidas na patogênese dos episódios reacionais da hanseníase, como fatores mantenedores.

Distribution of CD8 and CD20 lymphocytes in chronic periapical inflammatory lesions

O objetivo deste estudo foi o de investigar a distribuição de linfócitos CD8+ e CD20+ em lesões inflamatórias periapicais. Para tanto foram estudados 90 casos entre abscessos crônicos, cistos abscedados e cistos inflamatórios. A tecnica de imunohistoquímica pelo método da estreptavidina-biotina foi utilizada para identificar linfócitos T citotóxico/supressor (CD8) e linfócito B (CD20). Dentre os resultados encontrados notou-se uma distribuição das células CD8+ da seguinte forma: 1) difusa na capsula fibrosa dos abscessos crônicos (58,8 por cento) e ausente nos cistos abscedados (64,1 por cento) e cistos inflamatórios (70,6 por cento); 2) zona infiltrativa: difusa nos cistos abscedados (100 por cento) e cistos inflamatórios (82,4 por cento); 3) zona subepitelial: ausente nos cistos inflamatórios (53,0 por cento) e difusa nos cistos abscedados (56,4 por cento); 4) zona de supuração: difusa nos abscessos crônicos (100 por cento) e cistos abscedados (97,5 por cento). As células CD20+ apresentavam a seguinte distribuição: 1) cápsula fibrosa: ausente nos cistos inflamatórios (100 por cento), cistos abscedados (94,8 por cento) e abscessos crônicos (88,3 por cento); 2) zona infiltrativa: difusa nos cistos abscedados (100 por cento) e cistos inflamatórios (53 por cento); 3) zona subepitelial: ausente nos cistos inflamatórios (58,8 por cento) e focal nos cistos abscedados (46,2 por cento); 4) zona de supuração: difusa nos cistos abscedados (100 por cento) e abscessos crônicos (100 por cento). Em conclusão é possível afirmar que a distribuição linfocitária é predominantemente difusa para ambos os tipos de linfócitos.