Archivum Immunologiae et Therapiae Experimentalis

, Volume 67, Issue 6, pp 385–400 | Cite as

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

  • Yazan Ranneh
  • Abdah Md. AkimEmail author
  • Hasiah Ab. Hamid
  • Huzwah Khazaai
  • Norhafizah Mokhtarrudin
  • Abdulmannan Fadel
  • Mohammed H. K. Albujja
Original Article


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.


Animal model Chronic diseases Cytokines Lipopolysaccharide Multiple organs Systemic low-grade inflammation 





Chronic subclinical systemic inflammation


Tumor necrosis factor


Toll-like receptor


Tumor growth factor




C-reactive protein


Monocyte chemoattractant protein



This work was supported by Research Management Center at Universiti Putra Malaysia (Research Grant No. 05-01-11-1218RU). The authors would like to thank Faculty of Medicine and Health Sciences for the provision of their laboratory facilities and financial support. We would also like to thank the technicians in animal laboratory for their assistance in handling the animals.

Author Contributions

YR has designed research, performed experiments, interpreted data and wrote the manuscript. AMA has interpreted the data and supervised the work and helped in editing the manuscript. HAH, HK, and NM supervised the project and designed research. AF and MHKA edited the manuscript and interpreted data. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors have no competing interests to disclose.

Research Involving Human Participants and/or Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019

Authors and Affiliations

  1. 1.Department of Nutrition and Dietetics, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaUPM SerdangMalaysia
  2. 2.Department of Biomedical Sciences, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaUPM SerdangMalaysia
  3. 3.Department of Pathology, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaUPM SerdangMalaysia
  4. 4.School of Food Science and NutritionThe University of LeedsLeedsUK
  5. 5.Department of Forensic Biology, Faculty of Forensic SciencesNaif Arab University of Security SciencesRiyadhSaudi Arabia

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