Acta Dermato-Venereologica 97-10CompleteContent | Page 37

CORRESPONDENCE 1269 Microdialysis in Profiling Cytokines and Other Macromolecules in the Skin in Health and Disease: A Comment to Falcone et al. Bijar GHAFOURI 1 and Chris D. ANDERSON 2 1 Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, and 2 Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. E-mail: Chris.Anderson@regionostergotland.se The article by Falcone et al. (1) shows the outcome of a systematic review of human, minimally invasive techniques for the in-vivo measurement of interleukin 1a (IL-1α) and IL-1 receptor (IL1R). The search has been well performed according to the criteria of systematic review, but we take the opportunity to comment that the search terms for target macromole- cules are restrictive. Whilst these restrictions are to be lauded according to the authors’ current expert o pinion of the IL-1 family, the interests of researchers over the many years covered by the literature search may not have had similar knowledge (e.g. that it is more appropriate that IL-1α rather than IL-1β should be analyzed) or may have had entirely different interests as to relevant cytokines, biomarkers of other macromolecules. The result is, in our view, exclusion of valuable papers on the actually “minimally invasive” techniques because the “wrong” cytokines had been the subject of analysis. In order to illustrate what this might result in we have chosen our own “field of competence” microdialysis to generate an alternative (but because of space not exhaustive) view of which papers might be relevant for researchers (whether they be an individual PhD student or a research team leader) considering use of the techni- que for IL-1α/IL-1R or indeed any other biomarker/ macromolecule. The paper’s search technique yielded 3 articles on microdialysis which is but a fraction of e.g. a simple PubMed search of “microdialysis and cytokines” which yielded 143 peer reviewed articles of 4,042 human mi- crodialysis articles. Restriction of articles to publication in the present journal gives two articles of direct rele- vance to the authors motive for search (2, 3). A broader perusal of the work of the research groups actually referred to by Falcone et al. would also reveal further interesting articles. If we were to add our own favorite articles exemplifying use of microdialysis we would add papers covering correlation of microdialysis to histologic findings (4) and use in skin disease (5). In the paper by Hersini et al. (3) there are numerous articles referred to for their demonstration of cytokines in action (6, 7) or for their role over the years in elucidation basic principles of the technique (e.g. 8, 9). If we had been given the question ”Could microdia- lysis be used to collect quantifiable amounts of IL-11α, IL-1RA and other biomarkers from the skin causing no or minimal discomfort?”, we would have answered “Yes, without a doubt”. But the evidence for this is not provided adequately by the 3 articles surviving the cull in the review of Falcone et al. (1). In our view microdialysis is a sampling methodology with many advantages and is well established in studies of inflammatory mediators (3). Using microdialysis one has the opportunity to discard the samples reflecting the individual innate reactivity that is caused by tissue or blood sampling. Thus the in vivo milieu is more ac- curately reflected in samples obtained by microdialysis than by other methods. Additionally the microdialysate is a more “pure” sample. We are in full agreement with Falcone et al. (1) that we should try to measure in our target tissue the skin, the proteins involved in disease processes. We offer the content of this commentary as ancillary information on one of the techniques (microdialysis) reviewed in their article in the full knowledge that proponents of the other 7 techniques mentioned may well have similar views on useful papers that the article’s search methodology precluded. REFERENCES 1. Falcone D, Spee P, van de Kerkhof PCM, van Erp PEJ. Minimally- invasive sampling of interleukin-1α and interleukin-1 receptor antagonist from the skin: a systematic review of in vivo stu- dies in humans. Acta Derm Venereol 2017; 97: 1066–1073. 2. Sjögren F, Anderson C. Sterile trauma to normal human dermis invariably induces IL1b, IL6 and IL8 in an innate re- sponse to “danger” Acta Derm Venereol 2009; 89: 459-465. 3. Hersini H, Melgaard L, Gazerani P, Petersen L. Microdialysisi of inflammatory mediators in the skin: A review. Acta Derm Venereol 2014; 94: 501-511. 4. Sjögren F, Anderson CD. Are cutaneous microdialysis cytokine findings supported by end-point biopsy immunohistochem- istry findings? AAPS Journal 2010; 12: 741-749. 5. Sjögren F, Davidsson K, Sjöström M, Anderson CD. Cutaneous microdialysis; Cytokine evidence for altered innate reactivity in the skin of psoriasis patients? JAAPS 2012; 14: 187-195. 6. Averbeck M, Beilharz S, Bauer M, Gebhardt C, Hartmann A, Hochleitner K, et al. In situ profiling and quantification of cytokines released during ultraviolet B-induced inflammation by combining dermal microdialysis and protein microarrays. Exp Dermatol 2006; 15: 447–454. 7. Angst MS, Clark JD, Carvalho B, Tingle M, Schmelz M, Yeomans DC. Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and ad- ministration of a COX-inhibitor: a microdialysis study. Pain 2008; 139: 15–27. 8. Anderson C, Andersson T, Wardell K. Changes in skin circula- tion after insertion of a microdialysis probe visualized by laser Doppler perfusion imaging. J Invest Dermatol 1994; 102: 807–811. 9. Schmelz M, Luz O, Averbeck B, Bickel A. Plasma extravasation and neuropeptide release in human skin as measured by in- tradermal microdialysis. Neurosci Lett 1997; 230: 117–120. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340/00015555-2802 Acta Derm Venereol 2017; 97: 1269–1270