Transferrin and iron salts modulate differently tumor necrosis factor-alpha secretion by cultured human mononuclear cells

Iron is an essential element for the normal function of many biological pro cesses, including the immune response and hematopoiesis. Since iron deficie ncy results in impaired cytokine production (TNF-alpha), we investigated if iron, bound to its transport protein transferrin or by itself, modulates t he secretion of tumor necrosis factor-alpha (TNF-alpha) by circulating mono cytes. In particular, we examined the effect of Tf-bound iron or ferric chl oride (FeCl3) in the secretion of TNF-alpha by cultured blood mononuclear c ells (BMNC) obtained from women with either normal Fe status (n = 10) or wi th iron deficiency (n = 10). The addition of 30 mu M Tf, either in its apo or hole form, to BMNC cultures derived from both normal and iron deficient subjects, induced a marked increase in TNF-alpha secretion by cells, to abo ut 1.2-1.4 ng/mL. Similarly, the addition of CIM amounts of FeCl3, to norma l BMNC resulted in a dose-dependent increase of TNF-alpha secretion. By con trast, BMNC from iron deficient subjects were unable to secrete TNF-alpha u nder similar conditions. Lipopolysaccharide (LPS) induced a maximal secreti on of TNF-alpha (3.9 +/- 0.6 ng/mL, mean +/- SEM) in BMNC derived from bdh normal and iron deficient women, an indication that ID cells had the capaci ty to secrete TNF-alpha in response to a bacteriologic insult. However, the combined addition of LPS and iron-salt did nb induce a further increase in TNF-alpha secretion. These findings indicate that iron modulates the in vi tro secretion of TNF-alpha by human mononuclear cells through a process tha t depends both cn the iron status of the subject and on the form in which i ron is supplied. Moreover, transferrin also induces the secretion of TNF-al pha in a way apparently independent of its iron-donating capacity. (C) 1999 Elsevier Science Inc.