PBMC-derived FGF, PDGF, VEGF and GM-CSF secretion in endometriosis: a case-control in vitro study.

BACKGROUND: Endometriosis is a chronic inflammatory disease with immune dysregulation in which angiogenic, and hematopoietic mediators are thought to contribute to ectopic lesion establishment and persistence. Whether circulating immune cells are intrinsically primed to secrete higher levels of pro-angiogenic growth factors remains unclear. This study evaluated in vitro secretion of fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by peripheral blood mononuclear cells (PBMCs) from women with and without endometriosis.

METHODS: In a case-control design, women with laparoscopically and histopathologically confirmed endometriosis (n = 36) and laparoscopically confirmed controls without endometriosis (n = 44) were enrolled. PBMCs were isolated from peripheral blood and cultured for 24 h under basal conditions or after non-specific mitogenic activation with phytohemagglutinin (PHA, 5 μg/mL). Supernatant concentrations of FGF, PDGF, VEGF and GM-CSF were quantified using a multiplex bead-based immunoassay (Bio-Plex/Luminex). Between-group comparisons used nonparametric tests; univariate logistic regression explored associations with endometriosis status; and false discovery rate (Benjamini-Hochberg) adjustment was applied for multiple testing.

RESULTS: Baseline secretion of FGF, PDGF, VEGF and GM-CSF by PBMCs did not differ significantly between women with endometriosis and controls after correction for multiple comparisons. PHA stimulation induced marked shifts in secretion profiles across participants- characterized by increases in FGF, PDGF and VEGF and a decrease in GM-CSF-but neither stimulated concentrations nor percent changes differed significantly between groups following false discovery rate adjustment. In univariate logistic regression analyses, none of the baseline growth-factor measures significantly predicted the presence of endometriosis.

CONCLUSION: Under standardized in vitro culture conditions, PBMCs from women with endometriosis do not show a generalized increase in secretory capacity for the evaluated pro-angiogenic/hematopoietic growth factors compared with PBMCs from controls without endometriosis. These data do not support systemic PBMC hypersecretion of FGF, PDGF, VEGF and GM-CSF in endometriosis and are consistent with a compartmentalized model in which disease-relevant pro-angiogenic signaling is predominantly shaped within local peritoneal and lesion microenvironments.