Effects of intra-articular corticosteroids and anti-TNF therapy on neutrophil activation in rheumatoid arthritis

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 intraarticular 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 intraarticular 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.