Estrogen enhancement of anti-double-stranded DNA antibody and immunoglobulin G production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

Objective. To study the in vitro effect of estrogen on IgG anti-double-stra nded DNA (anti-dsDNA) antibody and total IgG production in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus ( SLE), in order to elucidate its regulatory role in SLE. Methods. PBMC from SLE patients and normal donors were cultured with 17 bet a-estradiol (E-2). IgG anti-dsDNA antibodies, total IgG, and cytokine activ ity in the culture supernatants were measured by enzyme-linked immunosorben t assay. Results, E-2 enhanced production of IgG anti-dsDNA antibodies as well as to tal IgG in PBMC from SLE patients. Anti-dsDNA production in patients with i nactive disease was less responsive to E-2 than that in patients with activ e disease. E-2 also enhanced total IgG, but not anti-dsDNA, production in t he PBMC of normal donors. Antibody production was increased by E-2 to a les ser extent in patients' B cells than in their PBMC. Anti-interleukin-10 (an ti-IL-10) antibodies partially blocked the E-2-induced increase in antibody production in patients' PBMC, but anti-IL-10 had no effect on B cells, E-2 increased IL-10 production by patients' monocytes, Exogenous IL-10 acted a dditively with E-2 in increasing antibody production in patients' B cells. Conclusion. These results suggest that E-2 may polyclonally increase the pr oduction of IgG, including IgG anti-dsDNA, in SLE patients' PBMC by enhanci ng B cell activity and by promoting IL-10 production in monocytes, These fi ndings support the involvement of E-2 in the pathogenesis of SLE.