Are cutaneous microdialysis cytokine findings supported by end point biopsy immunohistochemistry findings?

Abstract

Insertion of a cutaneous microdialysis catheter into normal dermis has been shown to induce the production of IL1b, IL6 and IL8 in an innate response to minimal trauma. In the present study, skin biopsy for immunohistochemistry has been performed at the site of the microdialysis catheter to compare the findings with that of the microdialysis findings 24 h after insertion. Of the three named cytokines, concordance between the two investigated technologies was highest for IL8 (100%) followed by IL6 (70%) and IL1b (50%). For seven other pro-inflammatory and T cell-relevant cytokines studied, concordance ranged between 50% and 80%. The total number of positive (microdialysis or immunofluorescence) findings was similar between the two methodologies. Technical and biological phenomenon can explain the differences. We conclude that both methodologies illustrate important features of tissue biology and that a combination of the two methods in clinical research can provide the chronology of soluble mediator participation and the more classic, but also more invasive, biopsy-based methodology at a point which constitutes the end of the observation period. We conclude further that at the 24-h time period here studied, microdialysis catheters are still functional and thus capable of producing relevant data which can be corroborated and extended by the "end point biopsy".

Fig. 1

Summary of the findings in all cutaneous microdialysis samples in ten healthy individuals for each of the ten cytokines over 24 h. The findings for each cytokine are the number of individuals: showing kinetics (rising and falling) of cytokine concentrations over time; for whom only a few samples had detectable concentrations; not having detectable cytokine concentrations in any sample

Fig. 2

a Median and range of total protein concentration (in μg/ml) in cutaneous microdialysis samples from ten individuals. The samples were collected hourly during the first 8 h, thereafter one sample collected during the following 5 h, one sample collected during the night and then again hourly collection the next morning until 24 h after catheter insertion. b Total protein concentration in (μg/ml) analysed in the cutaneous microdialysis sample collected the hour before biopsy, 24 h after catheter insertion. The figure shows the median and interquartile range for eight of the ten individuals

Fig. 3

A ×20 micrograph of an immunofluorescence stained section of a skin biopsy taken from the site where a microdialysis catheter membrane had lain for 24 h. The epidermis is uppermost. The red colour shows the location of the antibody directed against the cytokine IL6. The green colour shows the location of the antibody directed against a membrane antigen found on endothelial cells