Interleukin 10 (IL-10) is a key cytokine produced by a multitude of immune effector cells and possesses distinct regulatory effects on immune functioning in the skin. In this article we report the current understanding of the immunobiology of IL-10 and identify the role of IL-10 in cutaneous infection as well as in autoimmune and neoplastic processes. We reviewed the literature to examine the function of IL-10 in different cutaneous disorders. IL-10 can influence and potentially treat T1/T2 differentiation, antigen-presenting cell functioning, antigen-presenting cell–mediated T-cell activation, and T-cell, B-cell, and mast cell growth and differentiation that is aberrant in various disease processes. The literature consensus is that the multitude of effects of IL-10 contribute to the pathogenesis of different skin disorders. In certain circumstances IL-10 could represent novel therapeutic approaches to treating cutaneous diseases. Learning objective At the conclusion of this learning activity, participants should be acquainted with the role of IL-10 in many infectious diseases, autoimmune skin disease, inflammatory processes, and malignancy. Its possible role in the resolution of various skin diseases should be better understood.

https://www.jaad.org/article/S0190-9622(04)00251-8/pdf

The role of interleukin 10 in the pathogenesis and potential treatment of skin diseases.

Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease.

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The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease.

Background and Purpose—Although previous research reveals that cardiovascular events and thromboembolic diseases are important causes of death in patients with bullous pemphigoid (BP), the risk of ...

Increased Risk of Stroke in Patients With Bullous Pemphigoid A Population-Based Follow-Up Study

BACKGROUND Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid (BP) with contrasting results. OBJECTIVE To characterize Tregs and to determine the serum levels of regulatory cytokines in patients with BP. METHODS In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4(+) , CD25(+) , forkhead/winged helix transcription factor (FOXP3)(+) , transforming growth factor (TGF)-β(+) and interleukin (IL)-10(+) cells. In addition, the number of CD4(+) CD25(++) FOXP3(+) Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-β and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis (AD) and healthy donors. RESULTS The frequency of FOXP3(+) cells was significantly reduced in skin lesions from patients with BP (P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10(+) cells was lower in BP than in psoriasis (P < 0.001) and AD (P = 0.002), while no differences were observed in the number of TGF-β(+) cells. CD4(+) CD25(++) FOXP3(+) Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls (P < 0.001), and augmented significantly after steroid therapy (P = 0.001). Finally, TGF-β and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy (P = 0.01). CONCLUSIONS These data suggest that the depletion of Tregs and of IL-10 in patients with BP may be an important factor in the pathogenesis of the disease.

https://iris.unito.it/bitstream/2318/142764/4/142764_4aperto.pdf

Regulatory T cells in skin lesions and blood of patients with bullous pemphigoid.

Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with autoantibodies that recognize hemidesmosomal proteins. In addition to autoantibodies, the cell-mediated immune reaction is considered to play an important part in blister formation. Objectives To investigate some T-cell activation markers and inflammatory cytokines in the blister fluid and sera of patients with BP. METHODS: We measured soluble CD4 (sCD4) and soluble CD8 (sCD8), which have been, respectively, associated with CD4 and CD8 T-cell activation. Enzyme-linked immunosorbent assays were also used to quantify the production of the leucocyte chemoattractant interleukin (IL) -8 and of the cytokines IL-1alpha, IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha in the blister fluid and sera of 11 patients with BP.

RESULTS: The mean +/- SD level of sCD4 in patients' blisters (42.4 +/- 25.0 units mL-1) was significantly elevated (P < 0.005) compared with that in their sera (11.2 +/- 8.9) and that in the suction blisters of 10 healthy people (11.4 +/- 5.4; P < 0.005). Mean +/- SD IL-8 concentrations in BP blisters (4683.6 +/- 3878.1 pg mL-1) were much higher than those in their sera (17.1 +/- 18.9; P < 0.001), and were very significantly elevated (P < 0.005) in comparison with those in suction blisters of healthy persons (512 +/- 292). sCD4 levels in BP blisters were inversely related to IL-10 levels (P = 0. 03, r2 = 0.85), IL-8 levels were positively related to sCD8 levels (P = 0.01, r2 = 0.54), and IL-1beta levels were positively related to sCD8 concentrations (P < 0.005, r2 = 0.65).

CONCLUSIONS: The correlations suggest that there is a delicately orchestrated network of cytokines and cell-mediated immunity operating in BP blisters.

High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities.

Wong Tt

Papers

High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities.