Effect of hypertonic saline and macrophage migration inhibitory factor in restoration of T cell dysfunction

Purpose: Trauma-induced suppression of cellular immune function likely contributes to sepsis, multiple organ dysfunction syndrome and death. T cell proliferation decreases after traumatic stress. The addition of prostaglandin E2 (PGE₂), which depresses immune function after hemorrhage and trauma, to T-cells decreases T-cell proliferation; and hypertonic saline restores PGE₂-induced T-cell suppression. Recently, it has become apparent that macrophage migration inhibitory factor (MIF) plays a central role in several immune responses, including T-cell proliferation. However, the role of MIF in mediating hypertonic saline (HTS) restoration of T cell dysfunction is unknown. Therefore, we hypothesize that T cell immune restoration by HTS occurs, at least in part, by a MIF-mediated mechanism. Methods: Jurkat cells were cultured in Roswell Park Memorial Institute media, at a final concentration of 2.5 × 10⁶ cell/mL. The effects of HTS on T-cell proliferation following PGE₂-induced suppression were evaluated in Jurkat cells: HTS at 20 or 40 mmol/L above isotonicity was added. MIF levels were determined by enzyme-linked immunosorbent assay and western blot analysis. Results: PGE₂ caused a 15.0% inhibition of Jurkat cell proliferation, as compared to the control. MIF levels decreased in PGE₂-suppressed cells, as compared to the control. MIF levels were higher in cells treated with HTS than PGE₂-stimulated cells. Conclusion: The role of HTS in restoring Jurkat cells proliferation suppressed by PGE₂, at least in part, should be mediated through a MIF pathway.