Rheumatoid arthritis (RA) is characterized by the recruitment of leukocytes and 
the accumulation of inflammatory mediators within the synovial compartment. 
Release of the chemokine CCL18 has been widely attributed to antigen-presenting 
cells, including macrophages and dendritic cells. This study investigates the 
production of CCL18 in polymorphonuclear neutrophils (PMN), the predominant cell 
type recruited into synovial fluid (SF). Microarray analysis, semiquantitative 
and quantitative reverse transcriptase polymerase chain reaction identified SF 
PMN from patients with RA as a novel source for CCL18 in diseased joints. Highly 
upregulated expression of other chemokine genes was observed for CCL3, CXCL8 and 
CXCL10, whereas CCL21 was downregulated. The chemokine receptor genes were 
differentially expressed, with upregulation of CXCR4, CCRL2 and CCR5 and 
downregulation of CXCR1 and CXCR2. In cell culture experiments, expression of 
CCL18 mRNA in blood PMN was induced by tumor necrosis factor alpha, whereas 
synthesis of CCL18 protein required additional stimulation with a combination of 
IL-10 and vitamin D3. In comparison, recruited SF PMN from patients with RA were 
sensitized for CCL18 production, because IL-10 alone was sufficient to induce 
CCL18 release. These results suggest a release of the T cell-attracting CCL18 by 
PMN when recruited to diseased joints. However, its production is tightly 
regulated at the levels of mRNA expression and protein synthesis.