Abstract
Eicosanoids are lipid-mediator molecules with key roles in inflammatory skin diseases, such as psoriasis. Eicosanoids are released close to the source of inflammation, where they elicit local pleiotropic effects and dysregulations. Monitoring inflammatory mediators directly in skin lesions could provide new insights and therapeutic possibilities. Here, we analyzed dermal interstitial fluid samples obtained by dermal open-flow microperfusion in a rat model of skin inflammation. We developed a solid-phase extraction ultra-HPLC/MS/MS method to reliably and precisely analyze small-volume samples and quantified 11 eicosanoids [thromboxane B2, prostaglandin (PG) E2, PGD2, PGF2α, leukotriene B4, 15-HETE, 12-HETE, 5-HETE, 12-hydroxyeicosapentaenoic acid, 13-HODE, and 17-hydroxydocosahexaenoic acid]. Our method achieved a median intraday precision of approximately 5% and interday precision of approximately 8%. All calibration curves showed excellent linearity between 0.01 and 50 ng/ml (R2 > 0.980). In the rat model, eicosanoids were significantly increased in imiquimod-treated inflamed skin sites compared with untreated control sites. Oral treatment with an anti-inflammatory glucocorticoid decreased eicosanoid concentrations. These results show that a combination of tissue-specific sampling with LC/MS analytics is well suited for analyzing small sample volumes from minimally invasive sampling methods such as open-flow microperfusion or microdialysis to study local inflammation and the effect of treatments in skin diseases.
Highlights
Eicosanoids are lipid-mediator molecules with key roles in inflammatory skin diseases, such as psoriasis
During work on this publication C.P. and N.B. were employed at the Center for Biomarker Research in Medicine, C.P., B.R., T.B., F.S., M.B., and A.E. were employed at Joanneum Research Forschungsgesellschaft mbH, and K.E. and P.F. were employed at Sanofi
Thromboxane B2 (TXB2), prostaglandin (PG) E2, PGD2, PGF2, leukotriene B4 (LTB4), 15-HETE, 12-HETE, 5-HETE, 17-hydroxydocosahexaenoic acid (17-HDHA), 13-HODE, 12-hydroxyeicosapentaenoic acid (12-HEPE), and the multiple deuterated internal standards TXB2-d4, PGE2-d4, PGD2-d4, PGF2 -d4, LTB4-d4, 15(S)HETE-d8, 12(S)-HETE-d8, 5(S)-HETE-d8, and 13(S)-HODE-d4 were purchased from Cayman Chemicals (Ann Arbor, MI)
Summary
Eicosanoids are lipid-mediator molecules with key roles in inflammatory skin diseases, such as psoriasis. We analyzed dermal interstitial fluid samples obtained by dermal open-flow microperfusion in a rat model of skin inflammation. Oral treatment with an anti-inflammatory glucocorticoid decreased eicosanoid concentrations These results show that a combination of tissue-specific sampling with LC/MS analytics is well suited for analyzing small sample volumes from minimally invasive sampling methods such as open-flow microperfusion or microdialysis to study local inflammation and the effect of treatments in skin diseases.—Pipper, C., N. LC/MS/MS analyses of open-flow microperfusion samples quantify eicosanoids in a rat model of skin inflammation. Eicosanoids elicit local pleiotropic effects and dysregulations that occur in many severe diseases such as psoriasis, a common inflammatory skin disease [2,3,4,5].
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