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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 .