Induction of IgM and IgM-rheumatoid factor synthesis in vitro by indomethacin

Summary

Indomethacin, which is thought to exert its therapeutic effect by inhibiting the synthesis of PGE₂, is a commonly used first-line agent in the treatment of rheumatoid arthritis (RA). However, the effect of this drug on the humoral immune response in RA remains unclear. In this study, modulation of the in vitro synthesis of IgM and IgM-rheumatoid factor (RF) by indomethacin and prostaglandin E₂ was examined in 11 patients with active RA and 10 normal controls. Indomethacin at a final concentration of 1 μg/ml significantly enhanced IgM production (P<0.01) and RF production (P<0.02) inStaphylococcus aureus Cowan I (SAC) stimulated RA cultures when compared to controls in whom no net enhancement effect was observed. In the patients, this increase in IgM production was more pronounced than the corresponding increase in RF synthesis (P=0.078), suggesting that IgM and IgM-RF-secreting RA plasma cells have different susceptibilities to PGE₂ mediated suppression. Nonetheless, addition of PGE₂ (10⁻⁸ M final concentration) to the cultures inhibited IgM and RF production to a similar degree in the patient and control cultures. These findings demonstrate that PGE₂ causes suppression of IgM and IgM auto-antibody production in vitro and that inhibition of endogenous PGE₂ synthesis in RA patients treated with indomethacin results in a marked increase in the production of these antibodies.