IMMUNOLOGY LETTERS, cilt.105, sa.2, ss.140-149, 2006 (SCI-Expanded)
Previous reports from our group have established that the fetal ovine gamma globin chain (Hb gamma) and LPS can synergize in the induction of pro-inflammatory cytokines, especially TNF alpha, 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 Hb gamma 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 Hb gamma and LPS in TNFa 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 TNFa production which could be inhibited independently both by anti-Hb gamma and by anti-MIF, and optimally by a combination of these reagents. (c) 2006 Elsevier B.V. All rights reserved.