title: Interferon protects mice against inhalation anthrax.
abstract: Interferons (IFNs) play a role in innate immunity during many viral, bacterial, and protozoal infections. With the increasing threat of bioterrorist attacks with Bacillus anthracis, its high lethality, and the limited effectiveness of antibiotics, alternative treatments are being studied. Antibodies to protective antigen (PA) are promising, as is IFN. During many bacterial infections, production of and protection by IFNs has been reported, including B. anthracis in vitro. In vivo, we find that (1) the type I IFN inducer, Poly-ICLC, strongly and rapidly protects mice; (2) the protection is IFN-mediated since recombinant murine IFN-beta can protect, and protection by Poly-ICLC is abrogated in IFN type I receptor knockout mice. The greatest protection by Poly-ICLC was conferred by intranasal treatment. A delay in death was observed with the intramuscular route alone, but was not significant. Together, the results suggest the IFN defense could protect mice, up to 60%, against lethal inhalational anthrax, and thus have important medical implications for therapy of human anthrax.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1070, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Walberg
authors.forename: Samuel
authors.initials: S
authors.lastname: Baron
authors.forename: Joyce
authors.initials: J
authors.lastname: Poast
authors.forename: Barbara
authors.initials: B
authors.lastname: Schwartz
authors.forename: Lara
authors.initials: L
authors.lastname: Izotova
authors.forename: Sidney
authors.initials: S
authors.lastname: Pestka
authors.forename: J W
authors.initials: JW
authors.lastname: Peterson
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D001408:Bacillus anthracis / Q000276:immunology; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007369:Interferon Inducers / Q000008:administration & dosage*; D007370:Interferon Type I / Q000008:administration & dosage / Q000276:immunology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology; D007372:Interferons / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011070:Poly I-C / Q000008:administration & dosage* / Q000494:pharmacology; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011994:Recombinant Proteins; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000517:prevention & control
chemical_list: D007369:Interferon Inducers; D007370:Interferon Type I; D011994:Recombinant Proteins; D011107:Polylysine; C019531:poly ICLC; D007371:Interferon-gamma; D007372:Interferons; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C
references.citation: Infect Immun. 2002 Nov;70(11):6231-41
references.pmid: 12379702
references.citation: Antiviral Res. 1985;Suppl 1:173-83
references.pmid: 3936412
references.citation: Growth Factors. 2004 Dec;22(4):243-51
references.pmid: 15621727
references.citation: Antimicrob Agents Chemother. 2007 Apr;51(4):1373-9
references.pmid: 17296745
references.citation: Cytokine Growth Factor Rev. 2002 Apr;13(2):119-34
references.pmid: 11900988
references.citation: Infect Immun. 2004 Mar;72(3):1291-7
references.pmid: 14977930
references.citation: Curr Opin Immunol. 2000 Aug;12(4):419-24
references.pmid: 10899033
references.citation: Science. 1994 Jun 24;264(5167):1918-21
references.pmid: 8009221
references.citation: Emerg Infect Dis. 2001 Nov-Dec;7(6):933-44
references.pmid: 11747719
references.citation: Emerg Infect Dis. 2002 Oct;8(10):1066-72
references.pmid: 12396917
references.citation: J Transl Med. 2007 Feb 12;5:10
references.pmid: 17295916
references.citation: J Virol. 2005 Aug;79(16):10190-9
references.pmid: 16051812
references.citation: J Immunol. 2007 Mar 1;178(5):3126-33
references.pmid: 17312160
references.citation: Methods Mol Med. 2005;116:1-23
references.pmid: 16007741
references.citation: Infect Immun. 2006 Feb;74(2):1016-24
references.pmid: 16428748
references.citation: J Biol Chem. 2007 Jul 13;282(28):20047-51
references.pmid: 17502369
references.citation: J Toxicol Environ Health A. 2006 Jun;69(11):1083-95
references.pmid: 16840255
references.citation: Antimicrob Agents Chemother. 1972 Jan;1(1):80-1
references.pmid: 4670434
references.citation: PLoS One. 2007 Aug 15;2(8):e736
references.pmid: 17710136
references.citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7813-6
references.pmid: 16672361