Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet's disease (BD) and recurrent aphthous stomatitis is Th1-associated, although Th2-association is also observed in patients with BD

Abstract

Objective: Although the pathogenesis of Behcet's disease (BD) is unknown, immune dysfunction appears to be involved. To improve understanding of the role of T cells and cytokines in BD, the current study analysed the localization and extent of expression of T cell subsets, cytokines, chemokines, and chemokine receptors in oral ulcers from BD patients and for comparison in oral ulcers from patients with recurrent aphthous stomatitis (RAS), as well as in healthy oral mucosa.

Methods: Biopsies from oral ulcers of 25 BD patients and 19 RAS patients and oral mucosa from six healthy volunteers were immunoperoxidase stained.

Results: Both CD4- and CD8-positive T cells were present in the oral ulcers of BD and RAS patients. The T helper (Th)1 cytokines interleukin (IL)-12, interferon (IFN)-gamma, and tumour necrosis factor (TNF)alpha and the Th1-associated chemokine receptors CCR5 and CXCR3 were increased in both patient groups as compared to normal controls, indicating the involvement of a Th1 immune response in the immunopathology of both BD and RAS. However, the Th2 cytokine IL-4 was only observed in oral ulcers of BD patients but not in RAS patients.

Conclusion: This is the first study that shows the presence of pro-inflammatory cytokines, as well as Th1-associated chemokine receptors, in the oral ulcers of BD patients, as well as RAS patients, at a protein level. However, the expression of the Th2 cytokine IL-4 within the oral lesions of only BD patients is suggestive of a more complex antigenic stimuli in BD patients compared with RAS patients.