title: Effect of topical application of melatonin on serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with type 1 or type 2 diabetes and periodontal disease.
abstract: BACKGROUND
  The present clinical trial study was designed to assess the effect of topical application of melatonin on serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) in patients with diabetes and periodontal disease in comparison with healthy controls.
  
  
  METHODS
  Serum levels of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay and CRP by nephelometry by using the proper commercial kits in 30 patients with diabetes and periodontal disease, and also in a control group of 30 healthy subjects. Periodontograms were performed using the Florida Probe®. Patients with diabetes were treated with a topical application of melatonin (1% orabase cream formula) once daily for 20 days. Healthy subjects were treated with a placebo orabase cream.
  
  
  RESULTS
  Patients with diabetes and periodontal disease had significantly higher mean levels of serum TNF-α, IL-6 and CRP than healthy subjects (P < 0.001). Following topical melatonin application, there was a statistically significant decrease in the gingival index and pocket depth (P < 0.001) as well as a significant decrease in IL-6 and CRP serum levels (P < 0.001). Local melatonin application in patients with diabetes and periodontal disease resulted in a significant decrease in CRP and IL-6 serum levels as well as an improvement in the gingival index and pocket depth. Patients with periodontal disease had significantly higher serum CRP, IL-6 and TNF-α values by comparison with healthy subjects.
  
  
  CONCLUSIONS
  We conclude that melatonin can modulate the inflammatory action of these molecules in periodontal patients.
  
  
  BACKGROUND
  Melatonin, periodontal disease, diabetes mellitus, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, inflammatory markers.
authors.affiliation: Department of Special Care in Dentistry, School of Dentistry, University of Granada, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cutando
authors.affiliation: Department of Surgery, School of Dentistry, Faculty of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Montero
authors.affiliation: Department of Odontology, Faculty of Health Sciences, University of Alfonso X, Villanueva de la Cañada, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez-de Diego
authors.affiliation: Pinos Puente Healthcare Centre, Granada-Metropolitan Health District. Granada, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Ferrera
authors.affiliation: Department of Surgery, School of Dentistry, Faculty of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Valverde