Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

Despite relevant advances made in therapies for cardiovascular diseases (CVDs), they still represent the first cause of death worldwide. Cardiac fibrosis and excessive extracellular matrix (ECM) remodeling are common end-organ features in diseased hearts, leading to tissue stiffness, impaired myocardial functional, and progression to heart failure. Although fibrosis has been largely recognized to accompany and complicate various CVDs, events and mechanisms driving and governing fibrosis are still not entirely elucidated, and clinical interventions targeting cardiac fibrosis are not yet available. Immune cell types, both from innate and adaptive immunity, are involved not just in the classical response to pathogens, but they take an active part in “sterile” inflammation, in response to ischemia and other forms of injury. In this context, different cell types infiltrate the injured heart and release distinct pro-inflammatory cytokines that initiate the fibrotic response by triggering myofibroblast activation. The complex interplay between immune cells, fibroblasts, and other non-immune/host-derived cells is now considered as the major driving force of cardiac fibrosis. Here, we review and discuss the contribution of inflammatory cells of innate immunity, including neutrophils, macrophages, natural killer cells, eosinophils and mast cells, in modulating the myocardial microenvironment, by orchestrating the fibrogenic process in response to tissue injury. A better understanding of the time frame, sequences of events during immune cells infiltration, and their action in the injured inflammatory heart environment, may provide a rationale to design new and more efficacious therapeutic interventions to reduce cardiac fibrosis.

Neutrophils represent the primary defense against microbial threats playing a pivotal role in maintaining tissue homeostasis. This review examines the multifaceted involvement of neutrophils in periodontitis, a chronic inflammatory condition affecting the supporting structures of teeth summarizing the contribution of neutrophil dysfunction in periodontitis and periodontal-related comorbidities. Periodontitis, a pathological condition promoted by dysbiosis of the oral microbiota, is characterized by the chronic inflammation of the gingiva and subsequent tissue destruction. Neutrophils are among the first immune cells recruited to the site of infection, releasing antimicrobial peptides, enzymes, and reactive oxygen species to eliminate pathogens. The persistent inflammatory state in periodontitis can lead to aberrant neutrophil activation and a sustained release of proinflammatory mediators, finally resulting in tissue damage, bone resorption, and disease progression. Growing evidence now points to the correlation between periodontitis and systemic comorbidities. Indeed, the release of inflammatory mediators, immune complexes, and oxidative stress by neutrophils, bridge the gap between local and systemic immunity, thus highlighting neutrophils as key players in linking periodontal inflammation to chronic conditions, including cardiovascular diseases, diabetes mellitus, and rheumatoid arthritis. This review underscores the crucial role of neutrophils in the pathogenesis of periodontitis and the complex link between neutrophil dysfunction, local inflammation, and systemic comorbidities. A comprehensive understanding of neutrophil contribution to periodontitis development and their impact on periodontal comorbidities holds significant implications for the management of oral health. Furthermore, it highlights the need for the development of novel approaches aimed at limiting the persistent recruitment and activation of neutrophils, also reducing the impact of periodontal inflammation on broader health contexts, offering promising avenues for improved disease management and patient care.

Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response tonon-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity. Here we reviewed and discussed the role of NKs in selected, different, and “distant” chronic diseases, cancer, diabetes, periodontitis, and atherosclerosis, placing NK cells as crucial orchestrator of these pathologic conditions.

Peri-implant mucositis consists of a reversible inflammation of peri-implant tissues characterized by bleeding on gentle probing in the absence of bone loss. Ozone therapy is being extensively studied for its efficacy in treating different dental conditions. To date, few studies have evaluated ozone as an adjunct to the oral hygiene measures of peri-implant mucositis patients. The aim of the present study is to assess the efficacy of an ozonized gel (Trial group) compared to chlorhexidine (Control group) after a domiciliary protocol of oral hygiene in a 6-month study. According to a split-mouth study design, patients were divided into Group 1 for the application of chlorhexidine gel in peri-implant mucositis sites of quadrants Q1 and Q3, whereas in quadrants Q2 and Q4, the ozonized gel was in-office administered. For Group 2, the quadrants were inverted. At baseline (T0), and after 1 (T1), 2 (T2), and 3 (T3) months, Probing Depth (PD), Plaque Index (PI), SI Suppuration Index (SI), Bleeding Score (BS) and Marginal Mucosa Condition (MMC) were measured. A statistically significant decrease was found for all the variables assessed in each group (p < 0.05), whereas significant intergroup differences were found only for PI, BoP, and BS. Accordingly, both agents tested in this study showed an efficacy in treating peri-implant mucositis. The ozonized gel deserves particular attention, considering the better outcome than chlorhexidine on specific clinical periodontal parameters, as well as its lesser shortcomings.

Background. Tooth bleaching is the most frequently employed whitening procedure in clinics. The major side effect of tooth bleaching is dental sensitivity during and after the treatment. Here, we evaluated whether the administration of amorphous calcium phosphate (ACP), during in-office and at-home procedures may impact on dental sensitivity. Methods. Eighty patients, responding to the study requirements were enrolled according to the following criteria. Group 1 (n = 40), received in-office, 10% ACP prior to 30% professional hydrogen peroxide application. The whitening procedure continued at home using 10% carbamide peroxide with 15% ACP for 15 days. Group 2 (n = 40) received only 30% hydrogen peroxide application and continued the whitening procedures at home, using 10% carbamide hydroxide, without ACP- Casein phosphopeptides (CPP), for 15 days. Dental sensitivity was recorded with a visual analogue scale (VAS) at baseline, immediately after, and at 15 days after treatment in the two groups. Results. We observed that patients receiving ACP in the bleaching mixture experienced decreased dental sensitivity (* p ≤ 0.05), as detected by VAS scale analysis immediately following the procedures. Patients receiving ACP-CPP during at-home procedures showed a statistically significant (*** p ≤ 0.0001) reduction of dental sensitivity. Conclusions. We demonstrated that ACP-CPP administration, while exerting the same whitening effects as in control subjects receiving potassium fluoride (PF), had an impact on the reduction of dental sensitivity, improving patient compliance.