Furthermore, after B cell depletion therapy MPGES1, COX-1 and COX-2 levels in synovium of RA patients are essentially unaffected 4 weeks or 16 weeks after therapy despite clinical improvement in the majority of the studied patients. Also IL-1b and IL-6, strong inducers of MPGES1, did not change significantly. We showed that B cell depleting therapy exerts little effect on the PGE2 pathway enzymes, in agreement with our observation that B cells do not express these enzymes in the synovial tissue. However, B cells are important contributors to the inflammatory milieu in RA also by virtue of their capacity to activate T cells and secrete cytokines. Since COX-2 and MPGES1 Vindoline expression is inflammation-induced, a reduction of the B cell load in the rheumatoid tissue could in theory be followed by a Eupalinilide-D decrease in antibody and cytokine formation and a reduced interaction with other immune cells, leading to a decrease in their activity and infiltration. Indeed a recent study of the same cohort showed that rituximab induces a decrease in the number of synovial T cells, macrophages and more heterogeneously, plasma cells. In line with these changes, the inducible prostaglandin synthesis could have been affected. Of importance, our study showed that although achieving clinical improvement in a large percentage of the patients studied, rituximab did not change the local expression of MPGES1 and COX. Moreover, the variation in enzyme expression between the different time points did not reflect the change in synovial inflammatory cell populations, such as B cells, T cells, plasma cells and macrophages. In line, we found no clear cut decrease in the local expression of IL-1b and IL-6, even though these are produced by B cells, T cells and macrophages. Similarly, we have previously reported that anti-TNF agents do not suppress expression of MPGES1 or COX-2 in the rheumatoid synovium. Taken together, these data indicate that important inflammatory pathways are relatively unaffected despite rituximab mediated B-cell depletion and indirect decrease in other inflammatory cells.