Background: We previously reported that hemin-induced mitogenicity in mouse splenocytes was potentiated up to two-fold by interleukin (IL)-2, and the combination of hemin and IL-2 was also effective in inducing cytotoxicity for NK-resistant target cells. The purpose of this study was to investigate the effects of hemin both on expression of membrane surface receptors and on production of cytokine in human peripheral blood mononuclear cells (PBMC).
Methods: Human PBMC were obtained from 16 healthy volunteers. We analyzed hemin-mediated surface phenotypes of cells using flow cytometry, and levels of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the culture-supernatant of cells by ELISA system.
Results: Hemin induced increased expression of both transferrin receptor and IL-2 receptor (CD25) on PBMC in a dose-dependent manner. When the combination of hemin (30 mumol/L) and IL-2 (100 U/mL) was added to the culture of PBMC, the population of double positive cells was increased up to 70.4%. These effects of hemin were enhanced by the addition of catalase in the culture. Treatment with hemin plus IL-2 effectively enhanced the production of TNF-alpha and IFN-gamma in PBMC.
Conclusion: Hemin upregulated both IL-2 receptor and transferrin receptor expression, and stimulated TNF-alpha and IFN-gamma production in PBMC. IL-2 cooperated with hemin in eliciting these effects.