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J Pharmacol Toxicol Methods · Nov 2009
Comparative StudyProinflammatory tissue response and recovery of adipokines during 4 days of subcutaneous large-pore microdialysis.
- Trine Schnedler Clausen, Peter Kaastrup, and Bente Stallknecht.
- Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark. tcls@novonordisk.com
- J Pharmacol Toxicol Methods. 2009 Nov 1; 60 (3): 281-7.
IntroductionSubcutaneous adipose tissue (SAT) is increasingly being recognized as a highly active tissue secreting adipokines involved in many physiological and pathophysiological processes. Microdialysis is a technique used for in vivo sampling of interstitial fluid from e.g. SAT. The technique was originally designed for sampling of small molecules but recently the availability of catheters with large-pore membranes has made it possible to recover larger molecules such as adipokines. The present study investigated tissue response towards large-pore microdialysis catheters inserted into human SAT for 4 days.MethodsLarge-pore microdialysis catheters were inserted into the abdominal SAT of ten healthy males (age 23.0+/-1.1 years, BMI 22.1+/-0.7 kg/m(2), mean+/-SEM) and dialysates were collected immediately after insertion (day 0) and on days 1, 2 and 4. Dialysates were analyzed for IL-1beta, IL-6, IL-8, MCP-1, TNF-alpha and adiponectin using Luminex Multiplex technology.ResultsInterstitial IL-1beta increased from a sub-detectable level to 69+/-22 pg/ml on day 1 (p<0.001). IL-6 increased 23-fold on day 0 (p<0.001) towards a plateau of app. 5000 pg/ml on days 1 and 2. IL-8 increased 54-fold on day 0 (p<0.001) with further increase on day 1 (4259+/-777 pg/ml, p<0.001). MCP-1 increased 13-fold to an apparent plateau on day 0 (p<0.001) with further increase on day 1 (7256+/-1953 pg/ml, p=0.002). TNF-alpha increased 7-fold to an apparent plateau on day 0 (p<0.001) with further increase on day 1 (121+/-28 pg/ml, p=<0.001). By day 4, IL-1beta, IL-6, IL-8, MCP-1 and TNF-alpha were all returning towards baseline level. Adiponectin was unchanged on day 0 (1,040,422+/-295,510 pg/ml, p=0.36), decreased to 346,300+/-48,002 pg/ml on day 1 (p=0.002) and remained unchanged hereafter.DiscussionInsertion of a large-pore microdialysis catheter into human SAT results in tissue trauma leading to changes in the interstitial concentrations of IL-1beta, IL-6, IL-8, MCP-1, TNF-alpha and adiponectin.
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