Abstract
Indometacin farnesil (IMF) is a prodrug of indomethacin (IND) designed to reduce the occurrence of side-effects by esterification of the carboxyl group on IND with farnesol (FAR) . Previous studies have shown that IMF has characteristics of disease modifying anti-rheumatic drug in that it has a component of slow acting effect in treatment of rheumatoid arthritis patients. We therefore examined the effects of IMF on human B cells. Ig production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. At pharmacologically attainable concentrations, IMF, but not IND, suppressed the production of IgM and IgG. Of note, IMF, but not IND, showed additive suppressive effects on the B cell Ig production in the presence of either intramolecular disulfide form of bucillamine (SA-981) or gold sodium thiomalate. FAR showed similar suppressive effects on B cells to those of IMF.
These results indicate that IMF suppresses the human B cell functions by a different mechanism from that of bucillamine or gold sodium thiomalate. Thus, the data suggest that IMF may enhance the antirheumatic effects of bucillamine or gold sodium thiomalate.
