Cutaneous Application of Leukotriene B₄ as an in vivo Model of Psoriasis-Like Skin Inflammation: An Immunohistological Study

Abstract

Background: Research has revealed new insights into the pathogenesis of psoriasis, leading to new therapeutic options. So far the order of changes in the pathogenesis of psoriasis is unclear. The responses to cutaneous leukotriene B₄ (LTB₄) application have been studied in the past as an in vivo model for inflammation. The aim of the present study is to find out the order of changes of key steps in inflammation, which all have been shown to be involved in mature psoriatic lesions. Objective: To study the dynamics of the consecutive stages of inflammation in challenged skin as a reflection of a psoriasis-like inflammatory response. Methods: We examined the dynamics of epidermal growth control and the key representatives of the innate and acquired immune system during the first 72 h after challenging the skin by LTB₄ application. Results: Interleukin 17-positive (IL-17+) cells dominate the acute phase of inflammation, whereas T-Bet+ cells seem to increase gradually during the entire observation period. This indicates a more important role for IL-17 in the unstable phase of inflammation and a more prominent role for T-Bet+ cells within the chronic phase. Conclusion: The present model is highly reproducible and is useful in studying the dynamics of a psoriasis-like inflammation with respect to key components of immunity. It could provide a useful tool to study the immediate biological effects of new therapies like anti-IL-17 drugs on IL-17 production and effects on cutaneous inflammation and epidermal proliferation in vivo.

Response of the Endothelium to the Epicutaneous Application of Leukotriene B₄

“…Hendriks et al [28] reported the accumulation of inflammatory cells after LTB 4 challenge. An influx of neutrophils (elastase+ cells) was demonstrated only 8 h after LTB 4 application, coinciding with IL-17 accumulation followed by a decline after 32 h. This increase in inflammatory cells occurs concomitantly with acute endothelial changes.…”

“…One additional biopsy taken at baseline from unchallenged skin served as internal control. Biopsies were used from a previous study performed at our center [28]. …”

“…Topical application of LTB 4 on the skin has been used as an in vivo model for induced local skin inflammation [28]. This application causes a dose-dependent acute inflammatory response: initially, an accumulation of neutrophils followed by T-cell infiltration and epidermal proliferation.…”

Histamine Iontophoresis as in vivo Model to Study Human Skin Inflammation with Minimal Barrier Impairment: Pilot Study Results of Application of the Model to a Sensitive Skin Panel

“…No clinical signs of irritation were visible at time points later than 1 h. On the other hand, the lack of activation of Langerhans cells in the epidermis and of influx of T cells in the dermis, evidenced by the unchanged numbers of CD1a- and CD3-positive cells, respectively, confirms that this model (at least with the parameters chosen in this study) is not suitable for studying key mediators of adaptive immunity activated by sustained inflammation. For studying these mediators, other in vivo models such as tape stripping and application of leukotriene B 4 would be more appropriate [3,4,5]. …”

“…These models consist in the application of minimally invasive and standardized challenges to the skin, followed by evaluation of skin reactions at one or several points in time. Examples include tape stripping, consisting in repeated application of adhesive tape to mimic disruption of the skin barrier in disease or following skin-material interactions [3,4], and application of leukotriene B 4 to mimic psoriasis-like infiltration of immune cells in the epidermis [5]. In this study, we focus on one such in vivo model: histamine iontophoresis.…”