Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0408249 on November 26, 2008

Published online before print November 26, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow Buy
Right arrow All Versions of this Article:
jlb.0408249v1
85/3/582    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Döcke, W.-D.
Right arrow Articles by Volk, H.-D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Döcke, W.-D.
Right arrow Articles by Volk, H.-D.
(Journal of Leukocyte Biology. 2009;85:582-593.)
© 2009 by Society for Leukocyte Biology

Comprehensive biomarker monitoring in cytokine therapy: heterogeneous, time-dependent, and persisting immune effects of interleukin-10 application in psoriasis

Wolf-Dietrich Döcke*,1,2, Khusru Asadullah{dagger},1, Gudrun Belbe*, Merle Ebeling{dagger}, Conny Höflich*, Markus Friedrich{dagger},3, Wolfram Sterry{dagger} and Hans-Dieter Volk*

* Institute of Medical Immunology and
{dagger} Department of Dermatology, University Hospital Charité, Berlin Humboldt University, Berlin, Germany

2 Correspondence at current address: Bayer Schering Pharma AG, Target Discovery, D-13342 Berlin, Germany. E-mail: wolf-dietrich.doecke{at}bayerhealthcare.com

ABSTRACT

Cytokine and anticytokine treatments represent promising approaches for therapy of immune-mediated diseases. In humans, however, regulatory consequences of interference with the cytokine network are only partially understood. Biomarker analysis in clinical studies may help to overcome this complexity and provide novel information about the in vivo relevance of individual cytokines. We report systemic immunological effects of IL-10 therapy in 10 psoriasis patients during a 7-week treatment period followed by a 7-week observation period. IL-10 was given s.c. at 8 µg/kg/day or 20 µg/kg/3x/week, and a broad range of immunological biomarkers was analyzed in an extended kinetics (17 time-points) before, during, and after IL-10 therapy. Besides the expected anti-inflammatory effects (e.g., inhibition of LPS-induced cytokine secretion), we found unexpected effects, such as activation of NK cells and an increase in parameters indicating proinflammatory activity (C-reactive protein and soluble IL-2R). Furthermore, cumulative effects (IgE and IgA), loss of effect (IL-1R antagonist and IFN-{gamma} secretion), or counter-regulation during and rebound after IL-10 therapy (TNF-{alpha} and IL-12/IL-23 p40) were found. Remarkably, some alterations were retained long after the 7-week treatment period (IL-4 secretion, monocytic CD86, and TGF-β1). In summary, we found manifold effects of IL-10 far beyond the immediate anti-inflammatory activity considered initially. These findings may explain the rather disappointing clinical effects of IL-10 therapy in exacerbated inflammation but also hint to its role for sustained immunological reshaping. They further exemplify the importance of analyzing an extended kinetics of an entire panel of biomarkers for understanding the effects of therapeutic interference with the cytokine network.

Key Words: human • Th1/Th2 • inflammation • autoimmunity