Inter-α inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection.

Human inter-alpha-inhibitor proteins (IaIp) are endogenous human plasma proteins that function as serine protease inhibitors. IaIp can block the systemic release of proteases in sepsis and block furin-mediated assembly of protective antigen, an essential stop in the intracellular delivery of the anthrax exotoxins, lethal toxin and edema toxin. IaIp administered on hour or up to 24 hours after spore challenge with Bacillus anthracis Sterne strain protected mice from lethality if administered with antimicrobial therapy (p<.001). These human plasma proteins possess combined actions against anthrax as general inhibitors of excess serine proteases in sepsis and specific inhibitors of anthrax toxin assembly. IaIp could represent a novel adjuvant therapy for the treatment of established anthrax infection.