The role of tumor necrosis factor in sepsis

Spooner, Christopher; Markowitz, Norman; Saravolatz, Louis D.

doi:10.1016/0090-1229(92)90036-n

Cited by 120 publications

(72 citation statements)

References 37 publications

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“…Cytokines such as GM-CSF and interferon-gamma (IFN-gamma) have synergistic actions within this system. The observation that inhibiting the formation or the activity of TNF-alpha and/or IL-1 led to a reduction of endotoxin-or (Gram-negative) bacteria-induced sepsis mortality in different animal models underlined the role of this cytokine in the pathogenesis of sepsis and septic shock [3][4][5][6][7][8]. Studies on genetically manipulated mice with defined genetic deficiencies ("knock-out" mice) corroborated these findings.…”

Section: Sepsis -The Failure Of the Anti-inflammatory Therapeutic Strmentioning

confidence: 67%

Monocyte deactivation-rationale for a new therapeutic strategy in sepsis

et al. 1996

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Inflammatory cells, in particular monocytes/macrophages, release pro-inflammatory mediators in response to several infectious and non-infectious stimuli. The excessive release of these mediators, resulting in the development of whole body inflammation, may play an important role in the pathogenesis of sepsis and septic shock. TNF-alpha, acting synergistically with cytokines such as IL-1, GM-CSF and IFN-gamma, is the key mediator in the induction process of septic shock, as shown in several experimental models. Based on this concept and on the encouraging results obtained in several experimental models, a number of clinical sepsis trials targeting the production or action of TNF-alpha or IL-1 have been performed in recent years. Unfortunately, these trials have failed to demonstrate a therapeutic benefit. One reason for this may be the lack of exact immunologic analyses during the course of septic disease. Recently, we demonstrated that there is a biphasic immunologic response in sepsis: an initial hyperinflammatory phase is followed by a hypo-inflammatory one. The latter is associated with immunodeficiency which is characterized by monocytic deactivation, which we have called "immunoparalysis". While anti-inflammatory therapy (e.g. anti-TNF antibodies, IL-1 receptor antagonist, IL-10) makes sense during the initial hyperinflammatory phase, immune stimulation by removing inhibitory factors (plasmapheresis) or the administration of monocyte activating cytokines (IFN-gamma, GM-CSF) may be more useful during "immunoparalysis".

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Section: Sepsis -The Failure Of the Anti-inflammatory Therapeutic Strmentioning

confidence: 67%

Monocyte deactivation-rationale for a new therapeutic strategy in sepsis

et al. 1996

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“…IL-1β enhances the recruitment of inflammatory cells into airspaces and alters vascular permeability, leading to fluid transport and subsequent lung edema formation (Pugin et al 1996;Olman et al 2002). Because IL-6 is mainly produced in the lung, the level of IL-6 is a good index to assess the early injury of the lung (Spooner et al 1992). A study by Gultekin et al (2007) showed that leptin treatment ameliorated acute lung injury in rats by decreasing the production of pro-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats

Zhao

Wang

et al. 2015

J Histochem Cytochem.

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SummaryGlycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-κ B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-κB and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI. (J Histochem Cytochem 64:125-137, 2016)

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“…Septic shock is induced by bacterial release of endotoxins, which trigger intense production of proinflammatory cytokines, such as TNF-␣ that ultimately lead to multiorgan failure, including liver destruction. 9 We showed (Fig. 2B) that TNFR1⌬DD inhibited TNF-␣-dependent apoptosis of HeLa cells.…”

Section: Membrane-anchored Tnfr1 Decoys Protect Micementioning

confidence: 97%