F Sjögren1, C Svensson, C Anderson. 1. Institute for Biomedicine and Surgery, Department of Dermatology, and the Clinical Research Centre, Faculty of Health Sciences, University Hospital, 581 85 Linköping, Sweden.
Abstract
BACKGROUND: Cutaneous microdialysis in vivo in human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight. OBJECTIVES: To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis. METHODS: Use of a polyethylenesulphone membrane, with a cut-off value of 100,000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter. RESULTS: Reliable sample volumes and high analyte recovery were achieved either by push-pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments. CONCLUSIONS: Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.
BACKGROUND: Cutaneous microdialysis in vivo in human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight. OBJECTIVES: To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis. METHODS: Use of a polyethylenesulphone membrane, with a cut-off value of 100,000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter. RESULTS: Reliable sample volumes and high analyte recovery were achieved either by push-pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments. CONCLUSIONS: Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.
Authors: R Holmgaard; E Benfeldt; J B Nielsen; C Gatschelhofer; J A Sorensen; C Höfferer; M Bodenlenz; T R Pieber; F Sinner Journal: Pharm Res Date: 2012-03-15 Impact factor: 4.200