Periodontal diseases present a significant challenge to our healthcare system in terms of morbidity from the disease itself as well as their putative and deleterious effects on systemic health. The current method of diagnosing periodontal disease utilizes clinical criteria solely. These are imprecise and are somewhat invasive. There is thus significant benefit to creating a non‐invasive test as a method of screening for and monitoring of periodontal diseases, and, in particular, chronic periodontitis. Oral polymorphonuclear neutrophil (oPMN) counts have been found to correlate with extent of oral inflammation and the presence and severity of periodontal diseases. Potentially then, quantification of oPMNs might be used to identify and measure the severity of oral inflammation (oral inflammatory load; OIL) in subjects with healthy and inflamed periodontal tissues, demonstrating a positive correlation between higher oPMN counts and the extent/severity of OIL. These findings support the development and utilization of a non‐invasive chair‐side test enabling rapid, accurate, and objective screening of OIL based on measurement of oPMN numbers (similar to white blood cell levels in blood as used in medicine for assessment of infection). The use of such a test before, during, and after treatment of gingivitis and periodontitis could lead to improvements in timing of intervention (ie, when inflammation is active) thereby reducing long‐term morbidity.

Neutrophils are quickly recruited to tissues in response to proinflammatory cues; however, little is known about tissue neutrophil phenotypes in health. We employ a multicolor flow cytometric approach to assess surface markers of activation on neutrophils from the bone marrow, blood, peritoneum, spleen, liver, fat, colon, and oral cavity of healthy mice. Cell preparations were promptly fixed to preserve native surface marker expression levels. Peritoneal, colonic, and oral neutrophils were also assessed in the setting of pHrodo‐induced peritonitis, dextran sodium sulfate‐induced colitis, and ligature‐induced periodontal disease, respectively. Our results demonstrate consistent detectable neutrophil populations in various sterile and nonsterile tissues of healthy mice, and these cells had tissue‐specific neutrophil immunophenotypes. Neutrophils derived from biofilm‐associated mucosal tissues had 2‐ to 3‐fold higher expression of surface markers of activation, including CD66a, CD11b, and CD62L, compared to neutrophils derived from both sterile healthy tissues as well as tissues in animals treated with broad‐spectrum antibiotics. Furthermore, the unique cluster of differentiation (CD) marker activation signatures of tissue‐specific neutrophils from the peritoneum, colon, and oral cavity were altered to a proinflammatory immunophenotype with the presence of an inflammatory stimulus. Based on our results, we propose a model whereby a hierarchy of tissue neutrophil immunophenotypes, based on the differential expression of CD markers of activation, correlates with sterile, healthy commensal biofilm‐associated and inflamed tissue states.

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Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing tissues. It also plays a vital role in the development of neoplastic disorders. Pentoxifylline (PTX) is a vasoactive synthetic methyl xanthine derivative used for decades to manage chronic occlusive vascular disorders. Recently, it has been proposed that PTX might have an inhibitory effect on the angiogenesis process. Here, we reviewed the modulatory effects of PTX on angiogenesis and its potential benefits in the clinical setting. Twenty-two studies met the inclusion and exclusion criteria. While sixteen studies demonstrated that pentoxifylline had an antiangiogenic effect, four suggested it had a proangiogenic effect, and two other studies showed it did not affect angiogenesis. All studies were either in vivo animal studies or in vitro animal and human cell models. Our findings suggest that pentoxifylline may affect the angiogenic process in experimental models. However, there is insufficient evidence to establish its role as an anti-angiogenesis agent in the clinical setting. These gaps in our knowledge regarding how pentoxifylline is implicated in host-biased metabolically taxing angiogenic switch may be via its adenosine A2BAR G protein-coupled receptor (GPCR) mechanism. GPCR receptors reinforce the importance of research to understand the mechanistic action of these drugs on the body as promising metabolic candidates. The specific mechanisms and details of the effects of pentoxifylline on host metabolism and energy homeostasis remain to be elucidated.