Journal
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
Volume 87, Issue 5, Pages 369-372Publisher
WILEY
DOI: 10.1111/j.1365-2613.2006.00490.x
Keywords
cytokine; inflammatory response; MG-132; proteasome inhibitor; sepsis
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The Ubiquitin-proteasome system has recently been shown to be involved in the regulation of cytokine expression. We tested the hypothesis of whether the in vivo administration of proteasome inhibitor MG-132 can modulate cytokine response and mortality in sepsis. Sepsis was induced in mice by caecal ligation and puncture (CLP). Animals were divided into four groups: control, CLP, CLP and 1 mu g MG-132/g of b.w. intraperitoneally, and CLP and 10 mu g MG-132/g of b.w. Plasma levels of interleukin (IL)-1, tumour necrosis factor-alpha (TNF-alpha, IL-6 and IL-10 were determined by ELISA 6 h after the induction of sepsis. CLP induced significant increase in plasma levels of all measured cytokines. MG-132 treatment resulted in lower increase in IL-1, TNF-alpha and IL-10 levels. IL-6 was not significantly affected. A mortality study revealed prolonged survival in MG-132 treated mice. We conclude that MG-132 treatment decreases inflammatory response and prolongs survival in the CLP model of sepsis.
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