Walberg Kristin, Baron Samuel, Poast Joyce, Schwartz Barbara, Izotova Lara, Pestka Sidney, Peterson J W
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1070, USA.
J Interferon Cytokine Res. 2008 Oct;28(10):597-601. doi: 10.1089/jir.2007.0143.
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.
干扰素（IFN）在许多病毒、细菌和原生动物感染的先天免疫中发挥作用。随着炭疽杆菌生物恐怖袭击威胁的增加、其高致死率以及抗生素有效性的有限性，正在研究替代治疗方法。针对保护性抗原（PA）的抗体很有前景，干扰素也是如此。在许多细菌感染期间，已有关于干扰素产生和保护作用的报道，包括体外的炭疽杆菌。在体内，我们发现：（1）I型干扰素诱导剂聚肌胞苷酸-聚左旋赖氨酸-羧甲基纤维素（Poly-ICLC）能强烈且迅速地保护小鼠；（2）这种保护是由干扰素介导的，因为重组鼠干扰素-β能起到保护作用，且在I型干扰素受体基因敲除小鼠中，Poly-ICLC的保护作用被消除。通过鼻内给药，Poly-ICLC提供的保护作用最强。单独通过肌肉注射途径观察到死亡延迟，但不显著。总体而言，这些结果表明，干扰素防御机制可保护高达60%的小鼠免受致死性吸入性炭疽感染，因此对人类炭疽治疗具有重要的医学意义。
