Prostaglandin e2 modulation of rheumatoid factor synthesis

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Abstract
We examined the influence of prostaglandin E2 (PGE2) on the in vitro synthesis of rheumatoid factor (RF) by purified human B and T lymphocytes stimulated with Staphylococcus aureus Cowan 1 or pokeweed mitogen (PWM). Supernatants were assayed for total IgM and RF. PGE2 at concentrations of 10−7M to 10−9M significantly inhibited RF and IgM secretion stimulated by S aureus Cowan 1, a cross‐linker of B cell surface Ig. The magnitude of inhibition of RF production was significantly greater than that of total IgM at low PGE2 concentrations (P < 0.05). In contrast, PWM‐stimulated cultures were only minimally inhibited by PGE2 at all concentrations tested. Since cross‐linking of surface Ig renders B cells more susceptible to inhibition by PGE2, heat‐aggregated IgG (HAIgG) was added to the PWM‐stimulated cultures in an attempt to increase the sensitivity of precursors of RF‐secreting cells to the inhibitory effects of PGE2. Addition of HAIgG markedly increased PGE2‐mediated inhibition of RF synthesis without significantly affecting IgM production. Inhibition could not be overcome by the addition of soluble T helper cell factors, indicating that PGE2‐mediated suppression was not the result of an inhibitory action of T helper cells. When lymphocytes from patients with rheumatoid arthritis were examined, HAIgG was found to be unable to induce sensitivity to PGE2‐mediated inhibition of responsiveness. These results suggest that down‐regulation of RF synthesis requires both cross‐linking of surface Ig and the influence of PGE2. Abnormalities in this immunoregulatory mechanism may explain the ongoing production of RF in patients with rheumatoid arthritis.