Prolactin (PRL) has been shown to have immunoregulatory effects on a variety of immune responses. Its effect on B cell immune responses is suggested by in vitro data demonstrating a direct effect on B cell activation and differentiation, and also in vivo data demonstrating a biphasic stimulation of antibody production to sheep red blood cells. In addition, it has been shown both in animal models and patients with hyperprolactinemia that PRL may influence the presence of certain autoantibodies. The objective of this work was to study the effect of PRL on the induction of immunoglobulins, and anti-DNA and rheumatoid factor (RF) autoantibody production from peripheral blood mononuclear cells (PBMCs) from normal individuals and systemic lupus erythematosus (SLE) patients. Six female SLE patients and 10 normal individuals (5 females and 5 males) were studied. Ficoll-Hypaque-isolated PBMCs (1x10(6) cells/ml) with high concentrations of PRL (10(-4)-10(-8)M) and pokeweed mitogen (PWM) diluted to 1:400. An ELISA assay was used for immunoglobulins, RF and anti-dsDNA antibodies. PRL stimulated IgG and IgM production in a biphasic manner in normal PBMCs. Enhanced synthesis was observed at 10(-6) M, and a stimulatory effect was again observed at higher doses of PRL (10(-4))M. In contrast, only a mild stimulatory effect was observed in IgG synthesis by SLE PBMCs. These changes in Ig synthesis, however, did not reach statistical significance. PRL also induced IgG and IgM anti-dsDNA antibodies by both normal and SLE lymphocytes, but no differences were observed when compared to PWM stimulation. PRL induced IgM RF synthesis by normal lymphocytes but had no effect on SLE PBMCs. This study demonstrates that PRL induced immunoglobulin synthesis by normal and to a lesser degree by SLE lymphocytes, and also induced anti-dsDNA antibody by normal and SLE PBMCs, and IgM RF by normal PBMCs. However, the exact mechanism(s) of PRL action on the immune response awaits elucidation.