RESEARCH - Effects of intra-articular steroids and anti-TNF therapy on neutrophil activation in RA

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Published Online First: 12 January 2007. doi:10.1136/ard.2006.061507

ls of the Rheumatic Diseases 2007;66:1020-1025

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EXTENDED REPORT

Effects of intra-articular corticosteroids and anti-TNF therapy on

neutrophil activation in rheumatoid arthritis

Helmut Wittkowski 2,*, Dirk Foell 1,*, af Klint 4, Leen De Rycke

5, Filip De Keyser 5, Frosch 1, Ann- Ulfgren 4,

Johannes Roth 3

1 Department of Pediatrics, University of Münster, Germany

2 Interdisciplinary Centre of Clinical Research, University of Münster, Germany

3 Institute of Experimental Dermatology, University of Münster, Germany

4 Rheumatology Research, Karolinska University Hospital, Stockholm, Sweden

5 Department of Rheumatology, Ghent University Hospital, Ghent, Belgium

ABSTRACT

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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Read the full article here:

http://ard.bmj.com/cgi/content/full/66/8/1020

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