1066
SPECIAL REPORT ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Minimally-invasive Sampling of Interleukin-1α and Interleukin-1 Receptor Antagonist from the Skin: A Systematic Review of In vivo Studies in Humans
Denise FALCONE 1, Pieter SPEE 2, Peter C. M. VAN DE KERKHOF 1 and Piet E. J. VAN ERP 1
1
Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands, and 2 FibroTX LLC, Tallinn, Estonia
Interleukin-1α( IL-1α) and its receptor antagonist IL-1RA play a pivotal role in skin homeostasis and disease. Although the use of biopsies to sample these cytokines from human skin is widely employed in dermatological practice, knowledge about less invasive, in vivo sampling methods is scarce. The aim of this study was to provide an overview of such methods by systematically reviewing studies in Medline, EMBASE, Web of Science and Cochrane Library using combinations of the terms“ IL-1α”, IL-1RA”,“ skin”,“ human”, including all possible synonyms. Quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology( STROBE) checklist. The search, performed on 14 October 2016, revealed 10 different sampling methods, with varying degrees of invasiveness and wide application spectrum, including assessment of both normal and diseased skin, from several body sites. The possibility to sample quantifiable amounts of cytokines from human skin with no or minimal discomfort holds promise for linking clinical outcomes to molecular profiles of skin inflammation.
Key words: IL-1α; IL-1RA; stratum corneum; in vivo evaluation. Accepted May 22, 2017: Epub ahead of print May 24, 2017 Acta Derm Venereol 2017; 97: 1066 – 1073.
Corr: Denise Falcone, Department of Dermatology, Radboud University Medical Center, René Descartesdreef 1, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands. E-mail: denise. falcone @ radboudumc. nl
The primary function of the skin is to provide a physical barrier between the internal milieu and the external environment( 1, 2). In addition, the skin was more recently recognized to have strong immunological role( 3). Keratinocytes and resident skin cells, such as fibroblasts, mast cells, Langerhans cells and other dermal dendritic cells, have been shown to release a wide variety of mediators, both in the maintenance of tissue homeostasis( immune-surveillance) as well as in case of injury or pathogen invasion( 4). Among the most characterized mediators are interleukins( IL) belonging to the IL-1 family, namely IL-1α, IL-1β and their receptor antagonist IL-1RA( 5). These cytokines are among the first mediators to be released in acute or chronic skin inflammation and are involved in a wide spectrum of( skin) diseases( 4, 5). In this respect, blocking IL-1 activity for therapeutic purposes has entered clinical practice( 6). Of note, unlike IL-1β, IL-1α and IL-1RA have also been shown to be detectable in normal skin( 4).
Evidence for the presence of biologically active IL-1 in normal epidermis and stratum corneum( SC) emerged in the mid 1980s by means of bioassays, which measured the ability of IL-1 to augment proliferation of specific cell lines( e. g. murine thymocytes in the thymocyte co-stimulation assay) or to stimulate release of collagenase or prostaglandin from human dermal fibroblasts( 7, 8). Bioassays were limited by the impossibility of discriminating between IL- 1α and IL-1β as well as between IL-1 and other cytokines( 9), prompting some authors to cautiously refer to their findings as IL-1 or IL-1α“ like” material( 10). In the late 1980s these obstacles were overcome by the advent of monoclonal antibodies against IL-1α and IL-1β, allowing the 2 isoforms to be determined and distinguished with high sensitivity and specificity( 9). Since then, enzyme immunoassays( EIA) and enzyme-linked immunosorbent assays( ELISA) have become widely used for the evaluation of soluble analytes in biological samples( 11, 12). The major shortcomings of ELISA are that it allows the measurement of only one analyte at a time in a given sample and that it requires relatively large sample amounts( typically 100 µ l)( 13). Building on the principles of ELISA, in the late 1990s multiplex arrays were introduced with the purpose of measuring multiple analytes in the same sample at the same time( 13, 14). An example is constituted by multiplex bead-based assays, in which sets of microscopic colour-coded beads( microspheres) coated with capture antibodies for specific analytes are simultaneously used( 13, 14). By flow cytometric analysis, the signal coming from the different bead sets can be distinguished and the binding events between the detection antibodies and the analyte-capture antibody complex on each bead set can be quantified( 13, 14). Comparability analyses between ELISA and multiplex bead-based assays yielded positive results( 15).
Given the relevance of IL-1 in skin homeostasis and disease, different sampling methods, followed by the above-mentioned immunoassay quantifications, have been reported to analyse it. While taking skin biopsies remains the most widely used approach in clinical practice, successful attempts using less invasive sampling methods have been reported. The aim of this study was to provide an overview of such minimally invasive methods by systematically reviewing studies in which doi: 10.2340 / 00015555-2709 Acta Derm Venereol 2017; 97: 1066 – 1073
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.