Experimental Pathology Section, National Institute of Medical Sciences and Nutrition, Mexico City, Mexico.
Clin Exp Immunol. 2011 Apr;164(1):80-9. doi: 10.1111/j.1365-2249.2010.04313.x. Epub 2011 Jan 14.
Tuberculosis is a worldwide health problem, and multidrug-resistant (MDR) and extensively multidrug-resistant (XMDR) strains are rapidly emerging and threatening the control of this disease. These problems motivate the search for new treatment strategies. One potential strategy is immunotherapy using cationic anti-microbial peptides. The capacity of l-isoleucine to induce beta-defensin expression and its potential therapeutic efficiency were studied in a mouse model of progressive pulmonary tuberculosis. BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv or with a MDR clinical isolate by the intratracheal route. After 60 days of infection, when disease was in its progressive phase, mice were treated with 250 µg of intratracheal l-isoleucine every 48 h. Bacillary loads were determined by colony-forming units, protein and cytokine gene expression were determined by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively, and tissue damage was quantified by automated morphometry. Administration of l-isoleucine induced a significant increase of beta-defensins 3 and 4 which was associated with decreased bacillary loads and tissue damage. This was seen in animals infected with the antibiotic-sensitive strain H37Rv and with the MDR clinical isolate. Thus, induction of beta-defensins might be a potential therapy that can aid in the control of this significant infectious disease.
结核病是一个全球性的健康问题，耐多药（MDR）和广泛耐多药（XMDR）菌株迅速出现，威胁着这种疾病的控制。这些问题促使人们寻找新的治疗策略。一种潜在的策略是使用阳离子抗菌肽进行免疫疗法。本研究旨在探讨 L-异亮氨酸在诱导β-防御素表达方面的能力及其在进展性肺结核小鼠模型中的潜在治疗效果。BALB/c 小鼠通过气管内途径感染结核分枝杆菌 H37Rv 或 MDR 临床分离株。感染 60 天后，当疾病处于进展期时，每 48 小时通过气管内给予 250 µg L-异亮氨酸进行治疗。通过集落形成单位测定细菌载量，通过免疫组织化学和逆转录定量聚合酶链反应（RT-qPCR）分别测定蛋白质和细胞因子基因表达，通过自动形态计量学量化组织损伤。L-异亮氨酸的给药诱导了β-防御素 3 和 4 的显著增加，这与细菌载量和组织损伤的减少有关。这在感染抗生素敏感株 H37Rv 和 MDR 临床分离株的动物中均可见。因此，诱导β-防御素可能是一种潜在的治疗方法，有助于控制这种重要的传染病。
