Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Dietary lipids/cholesterol may modulate liver immune function. We have recently found that mouse F4/80 Kupffer cells are classified into phagocytic CD68 Kupffer cells and cytokine-producing CD11b Kupffer cells. We here investigate how a high-fat and/or high-cholesterol diet affects innate immune liver mononuclear cells. ⋯ Although the proportion of CD68 Kupffer cells decreased in HFCD mice, phagocytic activity of them was enhanced. Mice fed with HCD rather than those fed with HFD showed features closer to HFCD mice. Thus, enhanced function of mouse liver mononuclear cells is likely dependent on the liver cholesterol level, rather than the liver triglyceride level.
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Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. ⋯ These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.
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Randomized Controlled Trial
Influence of severity of illness on the effects of eritoran tetrasodium (E5564) and on other therapies for severe sepsis.
Disease severity varies widely in patients with severe sepsis. Eritoran tetrasodium (E5564), a TLR4 antagonist, blocks the binding of endotoxin and is being evaluated as a novel therapy for severe sepsis. This analysis aimed to assess the efficacy of eritoran based on severity of illness and similar effects in other recent sepsis trials. ⋯ Potential survival benefits of eritoran in severe sepsis patients were associated with high severity of illness. These findings were used to design a phase 3 trial. Similar treatment by severity-of-illness interaction was found in most recent sepsis trials.
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The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1 mice were atrophic and completely devoid of CD3 T cells and CD19 B cells. ⋯ Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1 mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis.