The Inhibition of Macrophage Migration Inhibitory Factor

Abstract

Summary

Analogs of EACA were capable of inhibiting the in vitro activity of macro-phage migration inhibitory factor (MIF). The most active analog of EACA in terms of MIF inhibition had four methyl groups separating an acetylated amino group from a free carboxyl group. This compound, acetylated 5-amino valeric acid, was capable of inhibiting completely MIF activity in vitro at a concentration of less than 10⁻⁶ M without demonstrating any appreciable anti-tryptic activity, even at 10⁻³ M. Anti-tryptically active EACA did not inhibit MIF except at very high concentrations (10⁻² M). Further, the most purified preparations of MIF obtained from aqueous extracts of thymus that we have studied contained no significant proteolytic activity upon denatured hemoglobin at pH 3-8. Therefore, we do not correlate anti-tryptic with anti-MIF activity in vitro.