Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.

中文翻译：

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间歇性团注脂多糖刺激的Sprague-Dawley大鼠慢性亚临床全身炎症的诱导。

慢性亚临床全身性炎症在刺激与心血管疾病，癌症，类风湿性关节炎，糖尿病和神经退行性疾病相关的几种慢性疾病中起关键作用。因此，开发慢性亚临床全身性炎症的体内模型对于研究病理生理学和测量所涉及的免疫调节剂至关重要。每周对雄性Sprague-Dawley大鼠进行三次腹膜内间歇性注射盐水或脂多糖（LPS）（0.5、1、2 mg / kg）的试验，持续30天。在不同时间点和研究结束时测量血液，生化和炎症介质。收集心脏，肺，肾脏和肝脏进行组织学评估。外周血白细胞的显着升高包括中性粒细胞，单核细胞，和淋巴细胞，以及中性粒细胞与淋巴细胞的比例。促炎介质水平[C反应蛋白，肿瘤坏死因子（TNF）-α，白介素（IL）-6，IL-1β和IL-8]以及生化特征（碱性磷酸酶，天冬氨酸转氨酶，丙氨酸氨基转移酶，γ-谷氨酰转移酶，肌酸激酶，肌酐和尿素）显着增加（P <0.05），并增加了单核细胞趋化蛋白1和TNF-β的表达。心脏，肺，肾和肝组织的组织病理学变化显示出变性，炎性灶和间质间隙中白细胞的细胞浸润，水肿，纤维化，凋亡和坏死的早期迹象。结论，