Salivary Colony Stimulating Factor-1 and Interleukin-34 in Periodontal Disease

Abstract

Background: Colony-stimulating factor (CSF)-1 and interleukin (IL)-34 are macrophage growth factors and regulators of osteoclastogenesis. Their potential involvement in periodontal disease is yet unknown. The aim of this study is to explore the presence of CSF-1 and IL-34 in whole saliva in relation to periodontal disease.

Methods: Protocol validation was assessed in saliva of healthy donors (n = 21) by enzyme-linked immunosorbent assay. Salivary CSF-1, IL-34, and matrix metalloproteinase (MMP)-8, a biomarker candidate of periodontitis, were determined in 48 patients (29 patients with periodontitis, 12 with gingivitis, and seven healthy patients) and related to the following clinical periodontal parameters: bleeding on probing, probing depth, clinical attachment loss, and plaque index. An additional separate group of patients with gingivitis (n = 21) and some of the patients with periodontitis (n = 11) were subjected to non-surgical periodontal treatment, whereupon changes in salivary CSF-1, IL-34, and MMP-8 levels were determined and related to periodontal outcome.

Results: Patients with periodontitis displayed higher CSF-1 and MMP-8 levels in saliva compared with healthy patients, and IL-34 levels were lower. A higher CSF-1/IL-34 ratio was observed in patients with periodontitis compared with healthy patients. There was a positive correlation between CSF-1 and MMP-8, which both correlated negatively to IL-34, in patients with gingivitis and periodontitis. Clinical periodontal parameters correlated positively with CSF-1, MMP-8, and with the CSF-1/IL-34 ratio, and negatively with IL-34 in patients with periodontitis. After treatment CSF-1 and MMP-8 levels decreased together with observed clinical improvement in patients with gingivitis.

Conclusion: CSF-1 and IL-34 are present in saliva and seem to have complementary roles in periodontal disease: IL-34 in steady-state and CSF-1 in inflammation.

Keywords: Gingivitis; inflammation; innate immune response; intercellular signaling peptides and proteins; periodontitis; saliva.