The effect of iron in different forms on the proliferative response to mitogen and ferritin content of human mononuclear leukocytes (MNL) was studied in vitro. Iron-loaded transferrin (FeTF) but not apotransferrin (apoTF) significantly enhanced the mitogenic response of MNL in serum-free culture. Removal of TF from serum markedly reduced its effectiveness as a serum supplement. This effect could be almost totally reversed when the serum was reconstituted with both iron and apoTF. Four forms of iron showed a stimulatory effect on ferritin synthesis in MNL in the increasing order : FeTF < iron nitrilotriacetate < iron citrate (molar ratio 1: 20) < iron citrate (1:1). The effect appeared to be correlated with their susceptibility to polymerization in aqueous solution. It is proposed that iron may a) enhance the mitogenic response of MNL, due probably to the physiological form of iron, FeTF, and b) stimulate ferritin synthesis, a protective reaction of the cell to toxic polymerized forms of the metal. lymphocytes ; transferrin ; iron ; ferritin It is well established that alterations of iron balance, particularly deficiency, adversely affect the capacity of humans and experimental animals to effect an immune response, although the underlying mechanisms involved have not been completely clarified . In attempts to understand such effects, the role of iron in cells of the immune system has been evaluated in vitro by measuring the response of lymphocytes to mitogen in the presence or absence of the metal. However, due to the requirement for serum (which contains iron) shown by lymphocytes in culture, results showing the effect of iron addition to such cultures cannot lead to unequivocal conclusions. Results
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