Blockade of tumour
necrosis factor (TNF) is an effective treatment in
rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory
cytokines may be of importance in the pathogenesis of RA and as possible targets for
therapy. In this study we investigated the effect of TNF blockade (
infliximab) on the synovial expression of
IL-15 in RA in relation to different cell types and expression of other
cytokines, to elucidate whether or not
IL-15 is a possible target for
therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint
synovitis before and after three infusions of
infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of
IL-15, TNF, IL-1alpha, IL-1ss and IFN-gamma, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis.
IL-15 expression was detected in all synovial biopsies taken at baseline. After
infliximab therapy, the expression of
IL-15 was increased in four patients and reduced in five. Synovial expression of
IL-15 was not correlated with any CD marker or with the presence of any other
cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to
therapy. Thus, in this study the synovial expression of
IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that
IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade.