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Effects of intra-articular corticosteroids and anti-TNF therapy on neutrophil activation in rheumatoid arthritis
  1. Helmut Wittkowski2,*,
  2. Dirk Foell1,*,
  3. Erik af Klint4,
  4. Leen De Rycke5,
  5. Filip De Keyser5,
  6. Michael Frosch1,
  7. Ann-Kristin Ulfgren4,
  8. Johannes Roth3
  1. 1Department of Pediatrics, University of Münster, Germany
  2. 2Interdisciplinary Centre of Clinical Research, University of Münster, Germany
  3. 3Institute of Experimental Dermatology, University of Münster, Germany
  4. 4Rheumatology Research, Karolinska University Hospital, Stockholm, Sweden
  5. 5Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
  1. Correspondence to:
    Dr Dirk Foell
    Institute of Experimental Dermatology, University of Münster, Röntgenstr. 21, D-48149 Münster, Germany; dfoell{at}


Objective: The pro-inflammatory calcium-binding protein S100A12 has been recently ascribed to the novel group of damage associated molecular pattern (DAMP) molecules. Serum levels of S100A12 reflect neutrophil activation during synovial inflammation. The aim of this project was to analyse the effect of intra-articular corticosteroids or systemic anti-TNF treatment on synovial expression and serum levels of S100A12 in rheumatoid arthritis (RA).

Methods: Serum and synovial tissue was obtained from 19 RA patients prior to and 2 weeks after intra-articular corticosteroid therapy. Serum was collected for 34 other patients, and in 14 of these patients synovial tissue was additionally obtained prior to and after 8 weeks of infliximab treatment. The expression of S100A12 was analysed by immunohistochemistry on frozen sections. Levels of S100A12 in serum were determined by ELISA.

Results: S100A12 serum levels were elevated in patients with active RA prior to therapy and decreased significantly in patients who responded to treatment in both patient groups, but not in non-responders. The synovial expression of S100A12 was reduced 2 weeks after successful intra-articular corticosteroid treatment. A similar decrease in local expression was found after 8 weeks of successful infliximab treatment.

Conclusions: Successful treatment of RA leads to downregulation of the DAMP protein S100A12. Expression and secretion of S100A12 is rapidly diminished after therapy with intra-articular corticosteroids or infliximab. Taking these findings together, decreasing serum concentrations of S100A12 could reflect alleviated synovial neutrophil activation during successful anti-inflammatory therapy in RA.

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  • * These authors contributed equally to this work.

  • Published Online First 11 January 2007

  • This work was supported by grants from the Interdisciplinary Centre of Clinical Research (IZKF), University of Münster, Foe2/026/04, the Gustav V 80 years foundation, the Swedish Association Against Rheumatism and the “Åke Wiberg” Foundation.

  • Competing interests: None.