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Updated: Jan 30, 2026

Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
[SPECIFICITY OF IMMUNE MODULATING EFFECT OF YERSINIA PESTIS ENDOTOXIN]
Abstract:
Literature and own data on mechanisms, of realization of lipopolysaccharide (LPS) toxic potential of Yersinia pestis in the conditions of a macroorganism are analyzed. 2 modifications of LPS are examined - temperature dependent changes of chemical structure of polymers and a change in their conformation under the effect of micro- and macroorganism factors. A special attention is paid to comparative study of toxic and immune modulating properties of the specified LPS forms. Both LPS forms are concluded to activate TLR4/MD2 receptor, inducing synthesis of 2 types of cytokines - pro-inflammatory and interferons. However, dominance of their signal pathways and cross-regulation of the transduced signal are mirrored, and as a result the initial form of LPS initiates interferon synthesis, and conformationally changed - pro-inflammatory cytokines. Results of the experiments are summarized in 2 schemes of signal transfer by TLR4/MD2 receptor under the effect of 2 forms of Y pestis LPS. Variations of cytokine-inducing properties of the initial and conformationally-altered forms of Y pestis LPS corresponds to the immune response of the organism at each stage of the infectious process: late inflammatory response by interferon type is characteristic for intracellular cycle of plague development, and pro-inflammatory cytokine hyper-production is observed at the terminal stage of infection-toxic shock.
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