Role of MIF and glutathione, in association with fetal ovine globin chain (Hbγ) and LPS, in induction of TNFα from cells of young and aged mice, and PBL from healthy human populations

Previous reports from our group have established that the fetal ovine gamma globin chain (Hbγ) and LPS can synergize in the induction of pro-inflammatory cytokines, especially TNFα, from mouse and human leukocytes. A fetal sheep liver extract (FSLE) which was observed to have marked immunoregulatory properties in vivo and in vitro had independently been observed to contain significant amounts of each of these molecules. However, the biological activity of this extract (hereafter FSLE) was not explained solely by its content of Hbγ and LPS, and independent analysis confirmed also the presence of migration inhibitory factor, MIF, and glutathione in FSLE. We have investigated whether MIF and the cellular anti-oxidant glutathione can further synergize with Hbγ and LPS in TNFα induction from human cells in vitro, and mouse cells activated in vivo/in vitro. Our data show that indeed there is evidence for such a synergy. Treatment or mouse cells with FSLE produced an enhanced TNFα production which could be inhibited independently both by anti-Hbγ and by anti-MIF, and optimally by a combination of these reagents.