Prostaglandin-mediated immunoregulation: reduced sensitivity of in vitro immunoglobulin production to indomethacin in rheumatoid arthritis.

Spontaneous and pokeweed mitogen (PWM) stimulated in vitro immunoglobulin production from peripheral blood mononuclear cells (PBMC) of control subjects and rheumatoid arthritis (RA) patients both receiving non-steroidal anti-inflammatory drugs (RA + NSAID) was measured by an enzyme linked immunosorbent assay (ELISA). Spontaneous IgG and IgM-RF production from the RA + NSAID was significantly higher than in control subjects. IgM production was also elevated but not significantly. Indomethacin (10(-6) - 10(-8)M) added to in vitro cultures failed to influence spontaneous production from either group. PWM stimulated IgG production was not significantly different between the two groups whilst IgM synthesis was significantly reduced in the RA individuals. IgM-RF production was observed only in the RA + NSAID group. Indomethacin inhibited PWM stimulated IgG and IgM production in control individuals but was significantly less potent on IgG, IgM and IgM-RF production from the RA + NSAID group. This reduction in the inhibitory effect of indomethacin correlated significantly with the high spontaneous immunoglobulin production and a low PWM stimulation index observed in the RA + NSAID group. Indomethacin had no significant effect on PWM stimulated PBMC proliferation in the rheumatoid individuals. These results suggest that B lymphocytes from some RA + NSAID are 'pre-committed' to produce immunoglobulins spontaneously in culture, possibly as a consequence of activation in vivo, and are therefore relatively insensitive to PWM stimulation. These B lymphocytes may have progressed beyond the immunoregulatory steps involving prostaglandins.