Experimental Models of Systemic Inflammation and Their Translational Potential in Rheumatology Research
Nikolskyi I.S., Nikolska V.V. , Protsenko G.O., Semenova Ya.-M.O.
Summary. Systemic inflammation is a complex pathophysiological process characterized by generalized activation of the immune system, excessive cytokine release, endothelial dysfunction, and the development of multi-organ alterations. It plays a pivotal role in the pathogenesis of infectious, autoimmune, and immune-mediated disorders, including rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Understanding the mechanisms of systemic inflammation is essential for the development of effective therapeutic strategies. Objective: to analyze current experimental models of systemic inflammation, their pathophysiological features, advantages and limitations, and to evaluate their relevance for studying immune mechanisms and developing pathogenetically based therapies in rheumatology. Materials and methods. A comprehensive literature review was conducted using PubMed, Medline, and Google Scholar databases. Experimental and review studies focused on major models of systemic inflammation—including endotoxin-induced endotoxemia, polymicrobial sepsis models (cecal ligation and puncture, cecal slurry, colon ascendens stent peritonitis), sterile inflammation models (zymosan, LPS), virus-like immune activation (polyinosinic-polycytidylic acid), and large animal models—were analyzed and systematized. Results and discussion. Experimental models of systemic inflammation reproduce key mechanisms of the generalized immune response, including activation of pattern recognition receptors (TLRs, NOD-like receptors, Dectin-1), induction of intracellular signaling pathways (NF-κB, MAPK), and the development of a cytokine cascade with increased levels of TNF-α, IL-1β, IL-6, and other mediators. Endotoxemia models (LPS) are highly reproducible but limited in clinical relevance, whereas polymicrobial sepsis models (CLP, cecal slurry, CASP) more accurately reflect human infectious conditions. Sterile inflammation models enable investigation of immune activation in the absence of pathogens. Large animal models provide high translational value due to their physiological similarity to humans. These models are widely used to study systemic immune dysregulation underlying rheumatic diseases and to evaluate novel therapeutic approaches, including immunomodulatory and cell-based therapies. Conclusions. Experimental models of systemic inflammation are essential tools for investigating the mechanisms of systemic immune responses and multi-organ dysfunction. Their application contributes to a deeper understanding of the immunopathogenesis of rheumatic diseases and provides a basis for the development of novel pathogenetically targeted therapeutic strategies.
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