Accumulated evidence suggests that prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). Moreover, a PRL-like molecule is secreted by normal human lymphocytes and acts as an autocrine growth factor for lymphoproliferation. The objective of this study was to explore the PRL-like peptide production by peripheral blood mononuclear cells (PBMC) from patients with SLE. We investigated the PRL secretion by PBMC from six female SLE patients and nine normal subjects (5 women and 4 men). Ficoll-Hypaque isolated PBMC (1 x 10(6) cells/ml) were cultured with and without maximal stimulatory doses of PHA (1 mg/ml) or PWM (1/200). At 72 h of culture supernatants were harvested and used to determine PRL immunoreactivity by a radioimmunoassay (NIDDK-reagents). Cell extracts and concentrated supernatants were prepared to determine PRL by Western blot analysis (NIDDK-reagents). SLE non-stimulated PBMC secreted significantly higher levels of PRL than normal non-stimulated PBMC (8.09 +/- 4.15 ng/ml vs. 3.48 +/- 2.36 ng/ml, P = 0.02 by Mann-Whitney test). High levels of PRL were secreted by SLE-PHA stimulated PBMC (6.88 +/- 4.53 ng/ml) and SLE-PWM stimulated PBMC (16.57 +/- 16.39 ng/ml) compared with normal-PHA stimulated PBMC (5.83 +/- 5.27 ng/ml) and normal-PWM stimulated PBMC (8.54 +/- 5.49 ng/ml), respectively, but the differences were not significant. The maximal production of PRL was found in PWM-stimulated lymphocytes in both groups. Cells extracts prepared from SLE non-stimulated and stimulated PBMC contained a 11 KDa PRL immunoreactive material. Concentrated supernatants from SLE non-stimulated and stimulated PBMC contained both a 11 KDa and a 24-27 KDa PRL immunoreactive material. Our data indicate that PBMC from patients with SLE have an increased production of PRL-like immunoreactive material. This PRL is released in vitro as two different molecular weight forms, and appears to be derived from B rather than T lymphocytes.