Original Research ArticleDithranol treatment of plaque-type psoriasis increases serum TNF-like weak inducer of apoptosis (TWEAK)
Introduction
Psoriasis is a common chronic inflammatory disorder with prevalence ranging from 0.1% to 11.0% in different populations [1]. The etiology of the disease is multifactorial and not fully known. According to recent suggestions, epidermal keratinocyte hyperproliferation and incomplete differentiation result from T-cell mediated autoimmune reaction [2], [3]. The disease is characterized by the coincidence of infiltration of the dermis with multiple immune cells and increased dermal vascularity. Angioproliferation seems to play a crucial role in the early stages of the development of psoriatic lesions [4]. Laporte et al. [5] demonstrated that spontaneous keratinocyte apoptosis is decreased in lesional skin in psoriasis. They suggested that this phenomenon could play a role in the induction of psoriatic hyperplasia. Moreover, psoriatic keratinocytes are extremely resistant to apoptosis compared with normal skin-derived keratinocytes [6].
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) was first described as a member of the tumor necrosis factor (TNF) superfamily in 1997 by Chicheportich [7]. The authors reported its ability of inducing apoptosis. TWEAK is a transmembrane protein which can be cleaved to generate a smaller, active form and become a cytokine. In physiologic conditions, by binding to its receptor (fibroblast growth factor-inducible 14 – Fn14), TWEAK can participate in tissue repair and regeneration after acute injury [8]. In chronic inflammatory conditions, the TWEAK/Fn14 pathway promotes chronic inflammation [7], pathological hyperplasia and angiogenesis [9]. Girgenrath et al. [8] demonstrated that TWEAK promoted proliferation of progenitor cells and inhibited their terminal differentiation. All of these disturbances can be observed in psoriatic skin lesions.
Dithranol (anthralin) is a successful method of treatment of exacerbated plaque psoriasis. Although it is one of the oldest available therapies for psoriasis, very little data on its mechanism of action can be found. Recently, it has been shown to exert its therapeutic effect by inducing keratinocyte apoptosis [10].
The data on the role of serum TWEAK in psoriasis are very limited. The aim of this study was to compare serum concentrations of TWEAK in psoriatic patients and in healthy control group. We also investigated the influence of topical treatment with dithranol on serum TWEAK concentrations and their relationship with clinical disease activity measured with PASI (Psoriasis Area and Severity Index).
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Patients
The study was carried out on 40 patients aged 18 to 84 with exacerbated plaque psoriasis, characterized in Table 1. The individuals with other types of psoriasis were excluded from the study. Neither topical nor systemic treatment for psoriasis had been used by the patients for a period ranging from 1 to several months. During the study all the patients were treated topically: initially with 5% salicylic acid ointment (until desquamation – a few days), followed by dithranol in three increasing
Results
We observed an over two-fold decrease in PASI following the treatment (Table 1) (p < 0.001). Baseline serum TWEAK concentrations (from 359 pg/ml to 984 pg/ml, median 668 pg/ml) were significantly higher than those in the healthy controls (from 329 pg/ml to 738 pg/ml, median 573) (Fig. 1). Topical treatment caused further increase in serum TWEAK (p < 0.001) (Fig. 1).
We observed a significant positive correlation between PASI and patients’ white blood cells (WBC) count, as well as between TWEAK
Discussion
In the present study we have demonstrated significantly increased serum TWEAK levels in patients with psoriasis compared with healthy subjects. High levels of TWEAK in exacerbated psoriasis can reflect its possible role in the pathogenesis of the disease. Increased serum TWEAK levels had been previously reported in psoriatic arthritis [17].
TWEAK is a multifunctional cytokine that has been reported to play an important role in many inflammatory disorders including Henoch–Schoenlein–purpura [13],
Conclusion
In the present study we demonstrated significantly increased serum levels of TWEAK in patients with exacerbated plaque psoriasis compared to the control group. After topical treatment with dithranol, the concentration of serum TWEAK increased even further, as compared to baseline. Our results indicate a potential dual role of TWEAK: a proliferation inducing effect in lower concentrations and a proapoptotic effect in high concentrations. Better results of topical treatment in psoriatic patients
Conflicts of interests
The authors declare no conflict of interests.
Financial disclosure
The study was supported by grant (113-49733) from Medical University of Bialystok, Poland.
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