The inhibition of macrophage migration inhibtory factor (38485)

Analogs of EACA were capable of inhibiting the in vitro activity of macrophage 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 antitryptic activity, even at 10-3 M. Antitryptically active EACA did not inhibit MIF except at very high concentrations (10-2M). 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.