IL-1β-induced Langerhans' cell migration and TNF-α production in human skin: Regulation by lactoferrin

Marie Cumberbatch, M. Bhushan, R. J. Dearman, I. Kimber, C. E M Griffiths

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)352-359
    Number of pages7
    JournalClinical and experimental immunology
    Volume132
    Issue number2
    DOIs
    Publication statusPublished - 1 May 2003

    Keywords

    • Cytokines
    • Dendritic cells
    • Epidermis
    • Inflammation

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