Skip to main content

Advertisement

SpringerLink
Log in

Cutaneous Microdialysis: Cytokine Evidence for Altered Innate Reactivity in the Skin of Psoriasis Patients?

  • Research Article
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Cutaneous microdialysis demonstrates cytokine production in living human skin. In the present study, microdialysis samples taken from uninvolved and lesional skin in three test subjects with psoriasis over 24 h have been investigated for cytokine content with a bead-based multiplex immunoassay from Luminex. Concentration curves for a set of Th1/Th2 and pro-inflammatory cytokines measured differed from a reference group of ten subjects without psoriasis. The time to return to near baseline values after innate insertion reactivity is between 9 and 16 h. Post-equilibration levels (17–24 h) for the three main cytokines elevated in the reference group were differentially elevated outside the range of the reference group for interleukin-1β (IL1β) and IL8 but not so for IL6. Two further cytokines, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α not generally elevated in the reference group, showed elevated values in the test subjects. Multivariate time series analysis (chemometry) showed that cytokine patterns for the individual test subjects often fell outside the 99% confidence intervals of a model generated from the reference group. In a clinical research situation, cutaneous microdialysis is feasible, gives generally higher cytokine levels than in the blood and generates interpretable data on an individual’s reactivity compared with a reference group. This may well prove useful in delineation of pathogenetic issues, selection of appropriate therapy and monitoring of subsequent response in inflammatory dermatoses such as psoriasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

REFERENCES

  1. Christophers E, Mrowietz U. The inflammatory infiltrate in psoriasis. Clin Dermatol. 1995;13:131–5.

    Article  PubMed  CAS  Google Scholar 

  2. Gelfand J, Feldman SR, Stern RS, Thomas J, Rolstad T, Margolis DJ, et al. Determinants of quality of life in patients with psoriasis: a study from the US population. J Am Acad Dermatol. 2004;51:704–8.

    Article  PubMed  Google Scholar 

  3. Nestle F, Kaplan D, Barker J. Psoriasis. N Engl J Med. 2009;361:496–509.

    Article  PubMed  CAS  Google Scholar 

  4. Sabat R, Sterry W, Philipp S, Wolk K. Three decades of psoriasis research: where has it led us? Clin Dermatol. 2007;25:504–9.

    Article  PubMed  Google Scholar 

  5. Lowes M, Bowcock A, Krueger J. Patogenesis and therapy of psoriasis. Nature. 2007;445(22):866–73.

    Article  PubMed  CAS  Google Scholar 

  6. Lowes M, Lew W, Krueger J. Current concepts in the immunopathogenesis of psoriasis. Dermatol Clin. 2004;22:349–69.

    Article  PubMed  CAS  Google Scholar 

  7. Nickoloff B. Skin innate immune system in psoriasis: friend or foe. J Clin Invest. 1999;104:1161–4.

    Article  PubMed  CAS  Google Scholar 

  8. Nickoloff B. The cytokine network in psoriasis. Arch Dermatol. 1991;127:871–84.

    Article  PubMed  CAS  Google Scholar 

  9. Nickoloff B. Cracking the cytokine code in psoriasis. Nat Med. 2007;13(3):242–4.

    Article  PubMed  CAS  Google Scholar 

  10. Griffiths C, Christophers E, Barker J, Chalmers R, Chimenti S, Krueger G, et al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol. 2007;156:258–62.

    Article  PubMed  CAS  Google Scholar 

  11. Anderson C, Andersson T, Boman A, Molander M. Cutaneous microdialysis for the measurement in vivo of the percutaneous absorption of organic solvents. Curr Probl Dermatol. 1996;25:37–46.

    PubMed  CAS  Google Scholar 

  12. Anderson C, Svensson C, Sjögren F, Andersson T, Wårdell K. Human in vivo microdialysis technique can be used to measure cytokines in contact reactions. Curr Probl Dermatol. 1995;23:121–30.

    PubMed  CAS  Google Scholar 

  13. Averbeck B, Beilharz S, Bauer M, Gebhardt C, Hochleitner K, Kauer F, 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;15:447–54.

    Article  PubMed  CAS  Google Scholar 

  14. Clough G. Microdialysis of large molecules. AAPS J. 2005;7(3):E686–92.

    Article  PubMed  CAS  Google Scholar 

  15. Clough G, Jackson C, Lee J, Jamal S, Church M. What can microdialysis tell us about the temporal and spatial generation of cytokines in allergen induced responses in human skin in vivo. J Invest Dermatol. 2007;234:443.

    Google Scholar 

  16. Krogstad A, Jansson P, Gisslèn P, Lönnroth P. Microdialysis methodology for the measurement of dermal interstitial fluid in humans. Br J Dermatol. 1996;134:1005–12.

    Article  PubMed  CAS  Google Scholar 

  17. Petersen L, Kristensen J, Bülow J. Microdialysis of the interstitial water space in human skin in vivo: quantitative measurement of cutaneous glucose concentrations. J Invest Dermatol. 1992;99:357–60.

    Article  PubMed  CAS  Google Scholar 

  18. Salgo R, Thaci D, Boehncke S, Diehl S, Hoffman M, Boehncke W. Microdialysis documents changes in the micromilieu of psoriatic plaques under continuous systemic therapy. Exp Dermatol. 2011;20:130–3.

    Article  PubMed  Google Scholar 

  19. Sjögren F, Svensson C, Anderson C. Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis. Br J Dermatol. 2002;146(3):375–82.

    PubMed  Google Scholar 

  20. Sjögren F, Anderson C. Sterile trauma to normal human dermis invariably induces IL1b, IL6 and IL8 in an innate response to “danger”. Acta Dermatol Venereol. 2009;89:459-465

    Google Scholar 

  21. Anderson C, Andersson T, Wårdell K. Changes in skin circulation after insertion of a microdialysis probe visualized by laser Doppler perfusion imaging. J Invest Dermatol. 1994;102:807–11.

    Article  PubMed  CAS  Google Scholar 

  22. Groth L, Serup J. Cutaneous microdialysis in man: effects of needle insertion trauma and anaesthesia on skin perfusion, erythema and skin thickness. Acta Derm Venereol. 1998;78(1):5–9.

    Article  PubMed  CAS  Google Scholar 

  23. Anderson C, Andersson T, Andersson R. In-vivo microdialysis estimation of histamine in human skin. Skin Pharmacol. 1992;5:177–83.

    Article  PubMed  CAS  Google Scholar 

  24. Sjögren F. Dermal cell trafficking: from microscopy to microdialysis [medical]: Linköping: Unitryck Sweden; 2005.

  25. Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol. 2007;19:3–10.

    Article  PubMed  CAS  Google Scholar 

  26. Gallo R, Taylor K, et al. Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependant on Toll-like receptor 4, CD44 and MD-2. J Biol Chem. 2007;282:18265–75.

    Article  PubMed  Google Scholar 

  27. Yamasaki K, Muot J, Taylor K, Cogen A, Audish D, Bertin J, et al. NLRP3/cryopyrin is necessary for interleukin-1b (IL-1b) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J Biol Chem. 2009;284:12762–71.

    Article  PubMed  CAS  Google Scholar 

  28. Martinon F, Burns K, Tschopp J. The inflammosome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-B. Mol Cell. 2002;10:417–26.

    Article  PubMed  CAS  Google Scholar 

  29. Matzinger P. The danger model: a renewed sense of self. Science. 2002;296:301–5.

    Article  PubMed  CAS  Google Scholar 

  30. Watanabe H, Gaide O, Pétrilli V, Martinon F, Contassat E, Roques S, et al. Activation of the IL-1b—processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 2007;127:1956–63.

    Article  PubMed  CAS  Google Scholar 

  31. Stenken J, Church M, Gill C, Clough G. How minimally invasive is microdialysis sampling? A cautionary note for cytokine collection in human skin and other clinical studies. AAPS J. 2010;12(1):73–78

    Google Scholar 

  32. Sjögren F, Anderson C. Are cutaneous microdialysis cytokine findings supported by end-point biopsy immunohistochemistry findings? AAPS J. 2010;12:741.

    Article  PubMed  Google Scholar 

  33. Barton G. A calculated response: control of inflammation by the innate immune system. J Clin Invest. 2008;118:413–20.

    Article  PubMed  CAS  Google Scholar 

  34. Bos J, de Rie M, Teunissen M, Piskin G. Psoriasis: dysregulation of innate immunity. Br J Dermatol. 2005;152:1098–107.

    Article  PubMed  CAS  Google Scholar 

  35. Chamian F, Krueger J. Psoriasis vulgaris: an interplay of T lymphocytes, dendritic and inflammatory cytokines in pathogenesis. Curr Opin Rheumatol. 2009;16(4):331–7.

    Article  Google Scholar 

  36. Lowes M. Increase in TNFa and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti CD11a). Proc Natl Acad Sci USA. 2005;102:19057–62.

    Article  PubMed  CAS  Google Scholar 

  37. Fulwyler M, McHugh T. Flow microsphere immunoassay for the quantitative and simultaneous detection of multiple soluble analytes. Methods Cell Biol. 1990;33:613–29.

    Article  PubMed  CAS  Google Scholar 

  38. Wold S, Kettaneh N, Fridén H, Holmberg A. Modelling and diagnostics of batch processes and analogous kinetic experiments. Chemometr Intell Lab Syst. 1998;44:331–40.

    Article  CAS  Google Scholar 

  39. Wold S, Sjöström M, Eriksson L. PLS in chemistry. In: Schleyer PvR, Allinger NL, Clark T, Gasteiger J, Kollman PA, Schaefer III HF, et al., editors. The encyclopedia of computational chemistry. Chichester: John Wiley & Sons; 1999. p. 2006–20.

    Google Scholar 

  40. Wold S. Cross-validatory estimation of the number of components in factor and principal components models. Technometrics. 1978;20:397–405.

    Google Scholar 

  41. Eriksson L, Johansson E, Kettaneh-Wold N, Trygg J, Wikström C, S W. Multi and megavariate data analysis, part I basic principles and applications. 2nd ed. Umetrics AB: Umea, Sweden; 2006.

  42. Varol A, Seifert O, Anderson C. The skin pathergy test: innately useful? AODR 302:155–168;2010.

    Google Scholar 

  43. Florin L, Knebel G, Zingrinao P, Wonderstrass B, Mauch C, Shorpp-Kistner M, et al. Delayed wound healing and epidermal hyperproliferation in mice lacking Jun B in the skin. J Invest Dermatol. 2006;126:902–11.

    Article  PubMed  CAS  Google Scholar 

  44. Mascia F, Cataisson C, Lee T, Theadgill D, Mariani V, Amerio P, et al. EGFR regulates the expression of keratinocyte derived granulocyte/macrophage colony-stimulating growth factor in vitro and in vivo. J Invest Dermatol. 2010;130:682–93.

    Article  PubMed  CAS  Google Scholar 

  45. Gasson J. Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood. 1991;77:1131–45.

    PubMed  CAS  Google Scholar 

  46. Sonderegger I, Iezzi G, Maier R, Schmitz N, Kurrer M, Kopf M. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J Exp Med 205:2281–2294; 2008.

    Google Scholar 

  47. O’Shea J, Murray P. Cytokine signaling modules in inflammatory responses. J Immunol. 2008;28:477–87.

    Google Scholar 

  48. Wilson J, Boniface K, Chan J, Mckenzie B, Blumenschein W, Mattson J, et al. Development, cytokine profile and function of human interleukin 17 producing helper T cells. Nat Immunol. 2007;8(9):950–7.

    Article  PubMed  CAS  Google Scholar 

  49. Bonifati C, Carducci M, Cordiali-Fei P, et al. Correlated increases of tumor necrosis factor-alpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients: relationships with disease severity. Clin Exp Dermatol. 1994;19:383–7.

    Article  PubMed  CAS  Google Scholar 

  50. Raychaudhuri S, Jiang W, Raychaudhuri S. Revisiting the Koebner phenomenon role of NGFand its receptor system in the pathogenesis of psoriasis. Am J Pathol. 2008;172:961–71.

    Article  PubMed  CAS  Google Scholar 

  51. Nordlind K, Thorslund K, Lonne-Rahm S. Expression of serotonergic receptors in psoriatric skin. Arch Dermatol Res. 2006;298:99–106.

    Article  PubMed  CAS  Google Scholar 

  52. Azmi J, Griffin J, Antti H, Shore R, Johansson E, Nicholson J, et al. Metabolic trajectory characterisation of xenobiotic-induced hepatotoxic lesions using statistical batch processing of NMR data. Analyst. 2002;127:271–6.

    Article  PubMed  CAS  Google Scholar 

  53. Appay A, van Lier R, Sallusto F, Roederer M. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry part A. 2008;73A:975–83.

    Article  Google Scholar 

  54. Valeyev N, Hundhausen C, Umezawa Y, Kotov N, Williams G, Clop A, et al. A systems model for immune cell interactions unravels the mechanism of inflammation in human skin. PLoS Comput Biol. 2010;6:1–22.

    Article  Google Scholar 

Download references

ACKNOWLEDGEMENTS

This work has been supported by the Swedish Psoriasis Foundation and the Welander Foundation. We thank Mats Fredriksson LARC University of Linköping for statistical advice and Peter Anderson for work with illustrations.

Conflict of Interests

The authors identify no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Division of Dermatology, University Hospital, Linköping University, Linköping, Sweden

    Florence Sjögren, Karin Davidsson & Chris D. Anderson

  2. Research Group for Chemometrics, Department of Chemistry, Umeå University, Umeå, Sweden

    Michael Sjöström

  3. Department of Dermatology, Linköping University, 581 85, Linköping, Sweden

    Chris D. Anderson

Authors
  1. Florence Sjögren
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karin Davidsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Sjöström
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chris D. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chris D. Anderson.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Fig. a

The findings of five pro-inflammatory cytokines in cutaneous microdialysis samples collected over 24 h from the uninvolved skin of three subjects with psoriasis (ps1, ps2, ps3) are shown. Samples were collected hourly except for the sample “13 h” which is the pooled sample collected during the night. The median and range of the reference group (black, n = 10) is also shown (JPEG 1421 kb)

Fig. b

The findings of five pro-inflammatory cytokines in cutaneous microdialysis samples collected over 24 h from the lesional skin of three subjects with psoriasis (ps1, ps2, ps3) are shown. Samples were collected hourly except for the sample “13 h” which is the pooled sample collected during the night. The median and range of findings from “normal” skin in a reference group (black, n = 10) is also shown (JPEG 1607 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sjögren, F., Davidsson, K., Sjöström, M. et al. Cutaneous Microdialysis: Cytokine Evidence for Altered Innate Reactivity in the Skin of Psoriasis Patients?. AAPS J 14, 187–195 (2012). https://doi.org/10.1208/s12248-012-9331-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12248-012-9331-z

KEY WORDS

Search

Navigation