Identification of an agent in cultures of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro.

When cultured in vitro, Aspergillus fumigatus generated a metabolite(s) with anti-phagocytic activity as tested by macrophage adherence to plastic and phagocytosis of particulate matter. The metabolite(s) appeared after 3 d culture and reached a peak concentration after 5-6 d. The action of the anti-phagocytic agent(s) was rapid (5-15 min) and appeared not to alter membrane permeability or cause rapid cell death. Treatment of stimulator spleen cells with the agent(s) inhibited their ability to induce alloreactive and major histocompatibility complex restricted cytotoxic T cells. The metabolite(s) was chloroform-soluble and separated into three biologically active compounds on thin-layer chromatography. These compounds were purified greater than 1000-fold and one of them was identified as gliotoxin, a known metabolite of A. fumigatus, based upon NMR and IR spectroscopy, mass spectrometry, biological properties and other data.