Neopterin, the Cell-Mediated Immune Response Biomarker, in Inflammatory Periodontal Diseases: A Narrative Review of a More than Fifty Years Old Biomarker

Abstract

Neopterin is a biomarker of the activation of cellular immunity. The purpose of this review is to summarise neopterin metabolism, methods of its detection, and its role in inflammation, focusing on periodontal inflammatory diseases. This derivative of guanosine is a non-enzymatic product of 7,8-dihydroneopterin oxidation caused by free radicals which protect activated macrophages from oxidative stress. Various methods, usually based on enzyme-linked immunosorbent essay, high-performance liquid chromatography, or radioimmunoassay were developed for the isolation of neopterin. A wide spectrum of diseases and conditions are known to affect neopterin levels, including cardiovascular, bacterial, viral, and degenerative diseases, as well as malignant tumours. Neopterin levels were found to increase in subjects with periodontitis, especially when the oral fluid and gingival crevicular fluid were evaluated. These findings confirm the role of activated macrophages and cellular immunity in periodontal inflammatory diseases. The gingival crevicular fluid and the oral fluid appear to be the most valuable biologic fluids for the evaluation of neopterin levels in periodontitis. For gingival crevicular fluid, neopterin can be determined as the concentration or the so-called total amount. Nonsurgical periodontal treatment was associated with a decrease in neopterin levels, but an increase was also reported, suggesting the possible role of macrophages in the resolution of the periodontal lesion.

IL-23/IL-17 axis levels in gingival crevicular fluid of subjects with periodontal disease: a systematic review

“…Inflammatory mediators are the most commonly studied type of biomarkers in periodontal diseases, and their importance lies in the fact that these molecules reflect the dynamics of inflammation, highlighting the innate and adaptive immune activity of the host [ 19 ] in response to microbial-associated molecular patterns (MAMPS) in the proinflammatory microenvironment of the gingival sulcus [ 20 ]. Among them, interleukin-23 (IL-23), and interleukin-17 (IL-17), have been investigated individually and together to elucidate their role in the pathogenesis of periodontal diseases [ 21 ].…”

Modulation of cell-mediated immunity during pregnancy in wild bonobos

“…Neopterin increases when cell-mediated immune responses are activated in response to infection and inflammation in humans and bonobos [27][28][29] and can be reliably measured in their urine, facilitating regular, non-invasive monitoring [30,31]. In humans, neopterin is used to track maternal immune responses and shifts in immunity during pregnancy.…”

Comparative Evaluation of Adipolin Expression in Gingival Crevicular Fluid and Serum of Healthy Subjects and Periodontitis Patients with and without Type 2 Diabetes Mellitus

“…Microbial products trigger the release of cytokines, the dysregulation of which, in serum, saliva, and gingival crevicular fluid (GCF), lead to the disease. The role of cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-α), interferon-γ (INF), adipocytokines, and many others have been proven in the progression of periodontitis [4][5][6][7]. The increased level of cytokines seen in periodontitis can aggravate existing conditions, like atherosclerosis, diabetes, or rheumatoid arthritis [8].…”