IL-1β-induced Langerhans’ cell migration and TNF-αproduction in human skin: regulation by lactoferrin

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Abstract
In mice, the roles of cytokines in the initiation of epidermal Langerhans’ cell (LC) migration are well documented; however, the mechanism of this response in humans is less well defined. The purpose of the present investigation was to examine the contribution of interleukin (IL)‐1β to human epidermal LC migration and to define further the mechanisms of this response. We demonstrate here that homologous recombinant IL‐1β administered intradermally to healthy human volunteers provides a stimulus for LC migration, with significant (P < 0·01) reductions in LC densities being observed at both 2 h and 4 h following treatment. At the later time‐point of 4 h, injection of IL‐1β was also accompanied by activation of those LC remaining in the epidermis. Analysis of fluid aspirated from suction blisters formed at injection sites revealed significant (P < 0·01) tumour necrosis factor (TNF)‐α production (2·99 ± 1·18 pg TNF‐α/mg protein; mean ± s.d. of n = 10) in response to IL‐1β treatment compared with saline control injections (0·90 ± 1·05 pg TNF‐α/mg protein). Prior topical application of human recombinant lactoferrin (LF), an iron‐binding protein found in exocrine secretions and skin, inhibited IL‐1β‐mediated LC migration and also compromised the production of TNF‐α protein as measured in suction blister fluids derived from each of the treatment sites. Taken together, these data demonstrate that IL‐1β is associated with both the stimulation of human epidermal LC migration and local TNF‐α production. Topical treatment with LF compromises both these responses. These data suggest that topical LF may potentially represent a novel therapeutic in the treatment of skin inflammation where TNF‐α is an important mediator.