Tumour necrosis factor-alpha transcription in transferrin-stimulated human blood mononuclear cells: is transferrin receptor involved in the signalling mechanism?

Transferrin (Tf) and tumour necrosis factor-alpha (TNF-alpha) participate in immune response regulation. We studied the capacity of Tf to modulate 'in vitro' TNF-alpha secretion, membrane expression and transcription by human blood mononuclear cells (BMNC). Women 25-45 years of age with normal iron status (n = 20) or with iron deficiency (ID, n = 20) due to gynaecological bleeding were studied. BMNC were incubated with different proportions of Fe-exempt and Fe-saturated Tf (apo-Tf:holo-Tf). Apo-Tf or holo-Tf uniformly induced TNF-alpha secretion in the cell supernatants from both groups. Nevertheless, cytokine levels were significantly lower in ID subjects. For all Tf-Fe saturations assayed, mean TNF-alpha levels varied between 1.4-1.6 ng/ml and 0.4-0.7 ng/ml for normal and ID women respectively (P < 0.001). The addition of apo-Tf enhanced TNF-alpha secretion in a dose-dependent manner, but the cytokine levels were lower in ID group. Tf did not induce pro-TNF-alpha expression in monocytes and lymphocytes from either group. Tf-treated cells from normal individuals expressed approximately two to three times more TNF-alpha mRNA than cells from ID subjects. Mean values ranged 96-110 atmol/ml in normal women and 24-31 atmol/ml in ID women for all Tf-Fe saturation levels tested (P < 0.001). These results show that Tf-induced TNF-alpha secretion is transcriptionally regulated. The impaired TNF-alpha transcription in cells from ID subjects indicates that the quality of the immune response is linked to the Fe status of mononuclear cells.