Abstract

Iron is an essential element for the normal function of many biological processes, including the immune response and hematopoiesis. Since iron deficiency results in impaired cytokine production (TNF-?), we investigated if iron, bound to its transport protein transferrin or by itself, modulates the secretion of tumor necrosis factor-? (TNF-?) by circulating monocytes. In particular, we examined the effect of Tf-bound iron or ferric chloride (FeCl 3) in the secretion of TNF-? by cultured blood mononuclear cells (BMNC) obtained from women with either normal Fe status (n=10) or with iron deficiency (n=10). The addition of 30 ?M Tf, either in its apo or holo form, to BMNC cultures derived from both normal and iron deficient subjects, induced a marked increase in TNF-? secretion by cells, to about 1.2-1.4 ng/mL. Similarly, the addition of ?M amounts of FeCl 3 to normal BMNC resulted in a dose-dependent increase of TNF-? secretion. By contrast, BMNC from iron deficient subjects were unable to secrete TNF-? under similar conditions. Lipopolysaccharide (LPS) induced a maximal secretion of TNF-? (3.9 ± 0.6 ng/mL, mean ± SEM) in BMNC derived from both normal and iron deficient women, an indication that ID cells had the capacity to secrete TNF- ? in responce to a bacteriologic insult. However, the combined addition of LPS and iron-salt did not induce a further increase in TNF-? secretion. These findings indicate that iron modulates the in vitro secretion of TNF-? by human mononuclear cells through a process that depends both on the iron status of the subject and on the form in which iron is supplied. Moreover, transferrin also induces the secretion of TNF-? in a way apparently independent of its iron-donating capacity.