Unexpectedly, MTX promoted the expression not only of known cell cycle-regulating genes leading to benefits like reduced FLS proliferation, but also induced expression of important RA disease mediators such as IL1A and CSF2. In a microarray study from 2007, MTX treatment of unstimulated immortalized RA synovial fibroblasts resulted in differential expression of 29 genes, the majority being upregulated, including IL1A and IL1B, which supports our findings [55]. Here, IL1B is linked to rheumatoid arthritis.