ABSTRACT
Background: The growing interest in the possibilities of macrophages modulation with therapeutic purposes promotes new approaches for periodontitis treatment. Aim: The aim of this randomized controlled open clinical study was to evaluate the early clinical and immunological effects of the long-course azithromycin as an adjunct to scaling and root planing in periodontitis. Methods: 50 patients (with stage I-III, grade A/B periodontitis) and 22 periodontally healthy volunteers as the reference group were recruited. Following scaling and root planing (SRP), the patients were randomly assigned to one of two treatment modalities: SRP only (n = 25) and adjunct azithromycin (Az) treatment (n = 25). The patients were monitored at baseline, and 30 ± 5 days after therapy. Clinical attachment loss (CAL), periodontal probing depth (PPD) and bleeding on probing (BoP) were evaluated. Secondary outcome measures included mean changes in single-positive CD68 + and CD163 + macrophages (Mφs) density and ratio, evaluated by immunohistochemistry, and IL1-ß, IL-6, IL-10, TGF-ß levels, detected by ELISA. Results: At 1 month both groups showed significant improvements of CAL, PPD and BoP, without significant added benefit in terms of CAL, PPD and BoP of Az. But Az increased the density of CD68 + and CD163 + Mφs (P < 0.0001), decreased the CD68+/CD163 + ratio (P = 0.043), decreased IL-1ß (P < 0.01), IL-6 (P < 0.001) levels, and increased IL-10 (P < 0.0001) and TGF-ß (P < 0.001) levels compared to SRP and periodontitis at baseline. Conclusion: The long course of Az demonstrated modulation of CD68 + and CD163 + Mφs towards M2 polarization, which may play a significant role in achieving favorable long-term treatment outcomes. ClinicalTrials.gov.
ABSTRACT
Introduction: Introduction: Tumor-associated macrophages are an important prognostic factor and have been shown to be associated with invasion and migration of various types of cancer. Unlike M1-macrophages, which have pro-inflammatory and anti-cancer activity, M2-macrophages are immunosuppressive, promoting the restoration of the intracellular matrix, and therefore they contribute to the tumor growth. The aim: To study the quantitative characteristic and localization of CD68+ and CD163+ M2-like TAM that infiltrate non-luminal HER2-enriched carcinomas of BC in the primary focus without metastases and in paired specimens with metastases in the lymph nodes, as well as the pathomorphological characteristics of this type of BC. Material and methods: The material of the study were intraoperative tissues of tumors and ipsilateral lymph nodes at radical removal of mammary glands. Immunohistochemical characteristics of the removed tumors (ER, PR, HER2, Ki67) were used to organize two groups of patients with primary BC according to the N1 / 0 status. Results: The statistical processing of the entire set of digital data confirmed a significant increase in CD68+TAM, but not CD163+M2 under metastatic conditions (p <0.0001), which may suggest an increase in M1-type TAM and their promotion of metastases in non-luminal HER2-enriched BC. Analysis of peculiarities of TAM localization showed that CD68+TAM was localized by clusters within the tumor nests and adjacent stroma, necrotized nests, whereas the typical localization of CD163+TAM M2-like macrophages predominated in the stroma and near the necrotic sites (where their quantitative characteristics coincide with those of CD68+TAM). This may indicate a relative predominance of M1 macrophages precisely in tumor nests. Along with the results on increased CD68+TAM (but not CD163+TAM) in metastases, it is possible to assume the contribution of M1 macrophages to the development / metastasis of BC, as prognosticated for other tumors. Conclusions: A significant decrease in the number of CD68+TAM in metastases of the lymph node as compared with the primary clusters of BC, along with the absence of correlations, may reflect other functions of TAM in the affected lymph nodes or change of the tumor type in the metastasis.
