Gliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains of Aspergillus and other fungi with diverse biological activities. It inhibits 20S proteasomal chymotrypsin activity (IC50 = 10 µM), blocking the degradation of IkappaBalpha and preventing the activation of NF-kappaB. Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils. It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC50s = 149 and 579 nM, respectively). Under reducing conditions, gliotoxin inhibits leukotriene A4 hydrolase (LTA4H, Cay-10007817) epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B4 (LTB4, Cay-20110) synthesis in neutrophils and monocytes. In vivo, gliotoxin (5 mg/kg) reduces LTB4 plasma levels and blocks peritoneal neutrophil infiltration in a mouse model of peritonitis induced by zymosan A (Cay-21175). It also inhibits geranylgeranyltransferase I and farnesyltransferase (IC50s = 17 and 80 µM, respectively).