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Elevated Levels of Interferon Gamma, Tumor Necrosis Factor  , Interleukins 2, 4, and 5, but Not Interleukin 10, Are Present in Recurrent Aphthous Stomatitis
Irene J. Buño, MD;
J. Clark Huff, MD;
William L. Weston, MD;
Dennis T. Cook, BS;
Sylvia L. Brice, MD
Arch Dermatol. 1998;134:827-831.
Objective To investigate our hypothesis that recurrent aphthous stomatitis (RAS), an inflammatory disease of the oral mucosa, is the result of an abnormal oral mucosal cytokine cascade leading to an enhanced cell-mediated immune response directed toward focal areas of the oral mucosa.
Design Prospective nonrandomized case-control study.
Setting Academic referral center
Patients For part 1, 21 patients with RAS and 7 control patients; for part 2, 6 patients with RAS and 6 control patients.
Intervention For study part 1, lesional and clinically normal oral mucosal biopsy specimens were obtained during an acute episode (within 72 hours of onset of ulcer) from 21 patients with RAS. Normal oral mucosal biopsy specimens were obtained from 7 healthy individuals, who served as controls. In study part 2, oral mucosal biopsy specimens were obtained from 6 RAS and 6 control patients at 24 and 48 hours after surgical trauma to those sites.
Main Outcome Measures Detection of the following messenger RNA (mRNA) types by use of semiquantitative reverse transcriptase polymerase chain reaction. For part 1, interleukins (IL) 2, 4, 5, and 10, interferon gamma, and tumor necrosis factor  were measured. For study part 2, IL-10 and interferon gamma were measured.
Results In part 1, elevated levels of IL-2, interferon gamma, and tumor necrosis factor mRNAs were detected in RAS lesions, consistent with a cell-mediated immune response. The IL-10 mRNA was not increased in RAS lesions. In addition, lower resting levels of IL-10 mRNA were detected in the clinically normal mucosa from patients with RAS, as compared with levels seen in the healthy controls. In part 2, at both 24 and 48 hours following trauma to the oral mucosa, the levels of mucosal IL-10 mRNA remained lower in patients with RAS than those observed in healthy controls, while interferon gamma mRNA levels were higher.
Conclusion Failure to suppress the inflammatory reaction initiated by trauma or other external stimuli, likely involving a functional deficiency of IL-10 in the oral mucosa, appears to be important in the pathogenesis of RAS.
From the Department of Dermatology, University of Colorado School of Medicine, Denver.
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