Inter-α inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection.
Human inter-α inhibitor proteins are endogenous human plasma proteins that function as serine protease inhibitors. Inter-α inhibitor proteins 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. Inter-α inhibitor proteins administered on hour or up to 24 h after spore challenge with Bacillus anthracis Sterne strain protected mice from lethality if administered with antimicrobial therapy (P < 0.001). 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. Inter-α inhibitor proteins could represent a novel adjuvant therapy for the treatment of established anthrax infection.
Infectious Disease Research Laboratory, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA. Steven_Opal@brown.edu
Steven M
SM
Opal
Yow-Pin
YP
Lim
Patricia
P
Cristofaro
Andrew W
AW
Artenstein
Noubar
N
Kessimian
David
D
Delsesto
Nicolas
N
Parejo
John E
JE
Palardy
Edward
E
Siryaporn
D000510:Alpha-Globulins / Q000627:therapeutic use*; D000818:Animals; D000881:Anthrax / Q000188:drug therapy*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use; D001408:Bacillus anthracis / Q000187:drug effects / Q000472:pathogenicity; D024841:Fluoroquinolones; D006801:Humans; D008099:Liver / Q000382:microbiology; D008297:Male; D051379:Mice; D000077266:Moxifloxacin; D011804:Quinolines / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology
D000510:Alpha-Globulins; D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; C011877:inter-alpha-inhibitor; D000077266:Moxifloxacin