title: Levamisole can modulate the serum tumor necrosis factor-alpha level in patients with recurrent aphthous ulcerations.
abstract: BACKGROUND
  Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor necrosis factor (TNF)-alpha is an important inflammatory mediator and a critical cytokine for adequate host defense. Our previous studies have shown that 14-43% and 59-63% of patients in the ulcerative stage of major, minor or herpetiform RAU have significantly higher than normal serum levels of interleukin (IL)-6 and IL-8, respectively. In this study, we examined whether RAU patients in the ulcerative stage had a significantly higher than normal serum level of TNF-alpha and assessed whether treatment with levamisole can modulate serum TNF-alpha levels in RAU patients.
  
  
  METHODS
  This study used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of TNF-alpha in 146 patients with RAU, nine patients with traumatic ulcers (TU), and 54 normal control subjects. Fifty-five RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml were treated with levamisole for 0.5-4 months and their serum TNF-alpha levels were measured after treatment.
  
  
  RESULTS
  We found that 29% (42 of 146) RAU patients as well as 39% (24 of 61) major type, 20% (14 of 69) minor type, and 25% (four of 16) herpetiform type RAU patients had a serum level of TNF-alpha greater than the upper normal limit of 7.4 pg/ml. The mean serum level of TNF-alpha in patients with RAU (9.1 +/- 1.0 pg/ml, P < 0.001), major type RAU (11.6 +/- 1.9 pg/ml, P < 0.001), minor type RAU (6.9 +/- 0.9 pg/ml, P < 0.005), or herpetiform type RAU (9.6 +/- 2.7 pg/ml, P < 0.001) was higher than that (3.8 +/- 0.2 pg/ml) in normal control subjects. The mean serum TNF-alpha level was significantly higher in patients with major type RAU than in patients with minor type RAU (P < 0.05) and was significantly higher in major type RAU patients in the exacerbation stage than in the post-exacerbation stage (P < 0.05). In 55 RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml, treatment with levamisole for a period of 0.5-4 months could significantly reduce the serum TNF-alpha level from 16.4 +/- 1.9 to 5.8 +/- 0.6 pg/ml (P < 0.001).
  
  
  CONCLUSIONS
  We conclude that a significantly higher than normal serum level of TNF-alpha can be detected in 20-39% of patients in the ulcerative stage of major, minor or herpetiform RAU. The serum TNF-alpha level may be associated with the severity and the stage of RAU. Levamisole can modulate serum TNF-alpha levels in RAU patients.
authors.affiliation: School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Andy
authors.initials: A
authors.lastname: Sun
authors.forename: Jeng-Tzung
authors.initials: JT
authors.lastname: Wang
authors.forename: Jean-San
authors.initials: JS
authors.lastname: Chia
authors.forename: Chun-Pin
authors.initials: CP
authors.lastname: Chiang
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000037:antagonists & inhibitors; D007978:Levamisole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000293:injuries; D019226:Oral Ulcer / Q000097:blood / Q000209:etiology; D012008:Recurrence; D013281:Stomatitis, Aphthous / Q000097:blood / Q000145:classification / Q000188:drug therapy*; D013283:Stomatitis, Herpetic / Q000097:blood / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D007978:Levamisole