Purchase this article with an account.
V. P. Saw, G. Galatowicz, V. L. Calder, J. K. G. Dart; Interleukin-13 and TNF-Alpha in Ocular Mucous Membrane Pemphigoid. Invest. Ophthalmol. Vis. Sci. 2007;48(13):387.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Mucous membrane pemphigoid (MMP) is characterized by an excessive fibrotic response to inflammation. Fibrogenesis is linked to Th2 type cytokines. IL-4 and IL-5 are elevated in MMP, but it is not known whether IL-13, a key pro-fibrotic mediator, plays a role in this disease. Tumour necrosis factor (TNF)-α is an important proinflammatory cytokine, and anti-TNF-α therapies are successful in other autoimmune diseases. The aim of this study was to investigate the role of IL-13 and TNF-α in ocular MMP.
Bulbar conjunctival biopsies from MMP patients were taken both during active disease (n=9) and following immunosuppressive treatment (n=3). Biopsies from 60-70 year old normal patients (n=5) served as controls. Conjunctival expression of IL-13 and TNF-α was evaluated by immunohistochemistry in 2µm GMA-embedded sections. Conjunctival fibroblasts were also cultured from the biopsies. To evaluate whether these cytokines increase activation of conjunctival fibroblasts, the effect of overnight incubation with IL-13 and TNF-α on the expression of HLA-DR, ICAM-1 and costimulatory molecules by cultured conjunctival fibroblasts was evaluated by flow cytometry.
Strong conjunctival stromal IL-13 staining was present in 8/9 active MMP biopsies and in 2/3 treated MMP biopsies. In comparison, normal conjunctiva showed weak or no stromal staining. Strong epithelial IL-13 staining was present in 5/5 normal, 4/9 active MMP and 2/3 treated MMP biopsies. TNF-α staining in the stroma, particularly associated with blood vessels, was seen in active disease but not following treatment. CD54 (ICAM-1) was expressed on 96% of normal conjunctival fibroblasts. Both TNF-α and IL-13 upregulated this staining intensity 10-fold, but IL-13 downregulated the number of CD54-positive cells to 42%. HLA-DR was expressed at low levels (14%) in both normal fibroblasts and in TNF-α treated cells. In the presence of IL-13, HLA-DR expression increased to 56%. TNF-α downregulated the expression of CD86 from 56% to 13-17%. Expression of CD 40 and CD80 did not change.
Stromal IL-13 appears to be present in both active ocular MMP and following immunosuppressive treatment, and may play a role in fibrosis in this disease. TNF-α is present in the stroma associated with vessels in inflamed ocular MMP. In cultured conjunctival fibroblasts, IL-13 upregulates HLA-DR and downregulates ICAM-1, while TNF-α downregulates CD86. The in-vitro effect of these cytokines on conjunctival fibroblasts suggests an immunomodulatory role in this disease.
This PDF is available to Subscribers Only