Effect of vitamin E on production of macrophage migration inhibitory factor (MIF) by macrophages

Abstract

Macrophage migration inhibitory factor (MIF), a putative cytokine involved in inflammatory and immune responses, was identified in rat peritoneal macrophages by Western blot analysis and its secretion into culture medium by enzyme-linked immunosorbent assay. To clarify the possibility of vitamin E as an immune modulator, we investigated the effect of vitamin E on MIF production in macrophages in response to calcium ionophore A23187 and lipopolysaccharide (LPS). Intraperitoneal injections of vitamin E (5 mg per rat) for 6 successive days resulted in a significant increase of alpha-tocopherol content in peritoneal macrophages. Alpha-tocopherol content of macrophages in vitamin E-treated rats was 478.3 +/- 90.7 ng/10(6) cells, whereas in control rats it was 1.5 +/- 0.5 ng/10(6) cells. For the control macrophages, total MIF content of the medium (2.5 x 10(6) cells/18 ml) without stimulation was 40.7 +/- 3.6 ng after 14 h culture, whereas stimulation with calcium ionophore A23187 (400 nM) and LPS (5.0 microg/ml) induced the elevation of MIF content to 65.9 +/- 7.5 ng and 74.3 +/- 10.4 ng, respectively (p < 0.05, n = 3). On the other hand, vitamin E-enriched macrophages without stimulation showed less MIF content (14.0 +/- 4.2 ng) than the control (p < 0.05, n = 3). Similarly, the increase of MIF of vitamin E-treated macrophages was significantly suppressed after stimulation with calcium ionophore A23187 or LPS, compared with the control macrophages (p < 0.01, n = 3). From analysis of intracellular MIF content by Western blot, we found no alteration of intracellular MIF content of vitamin E-macrophages, in contrast to the decreased content of control stimulated-macrophages, showing that vitamin E suppressed MIF secretion into the culture medium. Taken together, these results indicate that vitamin E may contribute to the regulation of inflammatory and immune responses through regulation of MIF secretion, possibly by modulating macrophage-membrane architecture.

Cunning factor: macrophage migration inhibitory factor as a redox‐regulated target

“…In the light of close functional homology of MIF with TRX proteins there could be a link between MIF and antioxidants. Indeed, the inhibiting effect of vitamin E on MIF production by macrophages has been reported 102 . Administration of recombinant TRX can reduce various inflammatory conditions 38 , 47 and this along with reported antagonistic relationships between TRX and MIF 49 raises a question whether TRX might be an endogenous antagonist of MIF, which could be used with therapeutic purposes.…”

Oxidoreductase macrophage migration inhibitory factor is simultaneously increased in leukocyte subsets of patients with severe sepsis

“…Also, intracellular MIF may play a role in tumorigenic processes, as significant increases of MIF mRNA and intracellular MIF protein also were observed in tumor tissue from lung adenocarcinoma patients [19] as well as pituitary adenomas patients [28]. Moreover, the influence of α-tocopherol on MIF induction and secretion could be of potential clinical relevance, as MIF secretion is suppressed by α-tocopherol in macrophages attenuating proinflammatory stimuli [31,32]. When added exogenously α-tocopherol accumulates in macrophages.…”