The role of tumour necrosis factor-alpha (TNF-alpha) in wound healing is not clear. Elevated levels of TNF-alpha have been observed in fluids from chronic wounds and have been shown to decrease over time during the healing process. Therapeutic antibodies such as infliximab can inhibit TNF-alpha activity. In this case series, we applied infliximab topically to eight patients with chronic ulcers of more than 4-month durations. The ulcers had multifactorial aetiology, with chronic venous insufficiency being the most prominent factor. All the ulcers had failed to respond to any previous conventional treatment. Infliximab was applied repeatedly to ulcers either as a 10 mg/ml solution and covered with an adhesive sheet or as a gel formulation (0.45, 1, or 4.5 mg/g) under a hydrofiber dressing/adhesive sheet. Improvement was assessed by measuring the percentage of change in the ulcer surface area. Seven of the eight patients (12 of 14 ulcers) responded to treatment with infliximab. After 4 weeks of treatment, surface area was reduced by more than 50% in 6 of the 14 treated ulcers. Within 8 weeks, five ulcers completely healed, while another four were reduced by more than 75% in size. Chronic, therapy-resistant leg ulcers responded well to repeated topical administration of a solution or a gel containing the TNF-alpha antibody, infliximab. Randomised controlled studies should be conducted to further evaluate the effect of topical infliximab on chronic wound healing.

Our findings indicate that demonstration of tissue-bound IgE deposits provides an additional useful criterion for diagnosis of BP and MMP in some patients. Prospective studies are needed to better correlate the presence of tissue-bound and circulating IgE autoantibodies and their specificity with distinct clinical features and course of BP and MMP.

Fibroblasts constitute an important source of cytokines during inflammatory processes in the skin. Interleukin-1 is a potent, pleiotropic cytokine that is induced in activated human dermal fibroblasts. Interleukin-1 further induces many inflammatory mediators, including the chemokine interleukin-8. As fibroblasts express both interleukin-1 and the interleukin-1 receptor complex, the cellular response may be enhanced by autocrine activation. Interleukin-1alpha and interleukin-1beta lack a signal peptide and are translocated at the plasma membrane using an alternative secretory pathway, which may involve ATP-binding cassette transporter proteins. We hypothesize that inhibition of this pathway prevents secretion of interleukin-1, thereby downregulating interleukin-1-dependent autocrine induction of interleukin-8. We used the ATP-binding cassette 1 transporter inhibitor glybenclamide, which has been previously shown to block interleukin-1beta secretion in human monocytes. Using enzyme-linked immunosorbent assay, we assessed the effect of glybenclamide on interleukin-8 production in human dermal fibroblasts. In interleukin-1beta-transfected human dermal fibroblasts, interleukin-8 was induced through an autocrine activity of interleukin-1beta. Glybenclamide disabled this activation loop and significantly reduced interleukin-8. In human dermal fibroblasts that were stimulated with tumor necrosis factor alpha to reach high interleukin-1 expression levels, glybenclamide similarly suppressed interleukin-8. In contrast, glybenclamide did not affect interleukin-8 production in cells stimulated with interleukin-1 only. Glybenclamide did not affect caspase-1 in fibroblasts, which was expressed as an inactive precursor form, irrespective of treatments with tumor necrosis factor alpha and/or glybenclamide. Using overexpressing, interleukin-1-transfected COS-1 cells, inhibition of interleukin-1alpha and interleukin-1beta secretion was directly demonstrated on Western blots. These results are consistent with glybenclamide preventing externalization of interleukin-1 and subsequent autocrine induction of interleukin-8 in human dermal fibroblasts. Acting through such a mechanism, ATP-binding cassette transporter inhibitors may downregulate inflammation locally.

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