Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis-A randomized, clinical trial

Clark, Matthew A.; Plank, Lindsay D.; Connolly, Andrew B.; Streat, Stephen; Hill, Andrew; Gupta, Ramesh C.; Monk, David; Shenkin, Alan; Hill, Graham L.

doi:10.1097/00003246-199810000-00016

Cited by 110 publications

(67 citation statements)

References 42 publications

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“…In ATTACH, there was a significant increase in death and heart failure hospitalization at 28 weeks in the patients who received infliximab 10 mg/kg. Although we cannot discount the possibility that the worsening heart failure observed in the ATTACH trial and the suggestion of worsening heart failure outcome seen in the RENAISSANCE trial both may have been related to excessive TNF antagonism or loss of the beneficial aspects of cytokine signaling, there are other possible explanations, including "TNF rebound" 20 and complement fixation, that may have contributed to worsening heart failure outcomes in the ATTACH trial. However, precise mechanistic explanations for the differences in outcomes in the ATTACH and RENEWAL trials are not known, and the above suggestions are speculative.…”

Section: Discussionmentioning

confidence: 92%

Targeted Anticytokine Therapy in Patients With Chronic Heart Failure

et al. 2004

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Background-Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. Methods and Results-Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction Յ0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (nϭ373) or subcutaneous etanercept in doses of 25 mg every week (nϭ375) or 25 mg twice per week (nϭ375). In RENAISSANCE, patients received placebo (nϭ309), etanercept 25 mg twice per week (nϭ308), or etanercept 25 mg 3 times per week (nϭ308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE (Pϭ0.17) or RECOVER (Pϭ0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative riskϭ1.1, 95% CI 0.91 to 1.33, Pϭ0.33). Conclusions-The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.

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Section: Discussionmentioning

confidence: 92%

Targeted Anticytokine Therapy in Patients With Chronic Heart Failure

et al. 2004

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“…7 It is involved in the inflammatory pathway upstream of tumor necrosis factor (TNF)-a and, like TNF-a, is crucial for LPS toxicity. 26 Like all DAMP molecules, CLP has a double role in the homeostasis of phagocytes. In a steady condition, it contributes to the regulation of the cytoskeleton, and it is released as a danger signal when phagocytes are activated.…”

Section: Introductionmentioning

confidence: 99%

Calprotectin in rheumatic diseases

Ometto

Friso

Astorri

et al. 2016

Exp Biol Med (Maywood)

136

105

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Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment. AbstractCalprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-a inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.

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“…Their plasma levels correlate significantly with the severity of septic shock and multiple organ failure (2,3,11), and they share many biological effects and have been implicated in several acute and chronic pathological states. However, attempts to blunt the systemic inflammatory response by blocking the effects of IL-1␤ or TNF-␣ with receptor agonists or antibodies in severe sepsis have not been successful in reducing overall mortality rate (5,20). Possible reasons for the ineffectiveness of these trials may include the following: 1) The biological functions of IL-1␤ and TNF-␣ overlap and can complement each other (8).…”

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confidence: 99%