Induction of Chronic Subclinical Systemic Inflammation in Sprague–Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide

Abstract

Induction of chronic subclinical systemic inflammation in sprague-dawley rats stimulated by intermittent bolus injection of lipopolysaccharide ABSTRACT 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-tolymphocyte 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.

Increased intestinal permeability with elevated peripheral blood endotoxin and inflammatory indices for e-waste lead exposure in children

“…Consistently, two experimental endotoxemia models have suggested that in humans, intravenous administration of endotoxin can increase peripheral neutrophils and plasma cytokines (Grigoleit et al, 2010;Taudorf et al, 2007). In addition, during intraperitoneal intermittent LPS injection, pro-inflammatory mediators including C-reactive protein, TNF-α, IL-1β, IL-6, and IL-8, as well as peripheral neutrophils, monocytes, and lymphocytes, were elevated in rats, indicating chronic subclinical systemic inflammation (Ranneh et al, 2019). However, the above changes of neutrophils and monocytes were shown in the endotoxemia or systemic inflammation models, whereas the participants in this study were healthy children.…”

Peripheral blood indicators of rats with adjuvant-induced arthritis in various correction schemes

“…Известно, что хроническое воспаление отражается увеличением лейкоцитов в периферической крови, в первую очередь нейтрофилов и моноцитов. Увеличивается также и соотношение нейтрофилов к лимфоцитам [1,7]. При ревматоидном артрите эндотелиоциты и клетки синовиальной оболочки поврежденных суставов экспрессируют медиаторы воспаления, такие как IL-1, IL-2, TNF-α и др.…”

“…В группе без лечения данный индекс также был низок, однако за счет значительного повышения уровня сегментоядерных нейтрофилов. Такая картина характерна для истощенного иммунитета, в результате чего высок риск вторичных бактериальных осложнений [7]. Лимфоцитарный индекс оказался пониженным в группах без лечения, c АСОН ORN2 и преднизолоном (начиная с 14-х су-Рис.…”

Imbalances in TCA, Short Fatty Acids and One-Carbon Metabolisms as Important Features of Homeostatic Disruption Evidenced by a Multi-Omics Integrative Approach of LPS-Induced Chronic Inflammation in Male Wistar Rats

“…Additionally, besides the need for a deeper understanding of chronic inflammation, there is a strong need to target accurate animal models that reflect the biochemical and metabolic manifestations of the homeostatic disruption, which is generated by chronic inflammation. In this sense, a variety of studies have developed models to mimic acute or chronic inflammation using chemical or biological stimuli [ 13 , 14 ]. However, the isolation of chronic inflammation is challenging because it appears concomitantly with other conditions, and it does not exist separately in humans.…”

“…However, the isolation of chronic inflammation is challenging because it appears concomitantly with other conditions, and it does not exist separately in humans. Experimentally, one of the preferred stimuli for inducing chronic inflammation is the administration of lipopolysaccharide (LPS), a structure found in the outer membrane of gram-negative bacteria, which could be injected either intravenously or intraperitoneally, with different doses and frequency [ 14 , 15 , 16 , 17 ]. Furthermore, adjustment of administration, dose and frequency, together with additional approaches, allowed the development of different models of chronic inflammation diseases (e.g., CVDs or NAFLD) [ 18 , 19 ].…”