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Journal ArticleDOI

The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome.

Charles A. Dinarello
- 01 Jun 1991 - 
- Vol. 163, Iss: 6, pp 1177-1184
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TLDR
Use of neutralizing antibodies to TNF or to IL-1 receptors have reduced the consequences of infection and inflammation, including lethal outcomes in animal models.
Abstract
Treating the septic shock syndrome with antibodies that block only endotoxin has its limitations. Other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a, platelet-activating factor antagonists, and blockade of endothelial cell leukocyte adhesion molecules. Specific blockade of the proinflammatory cytokines interleukin-1 (IL-1) or tumor necrosis factor (TNF) reduces the morbidity and mortality associated with septic shock. Moreover, blocking IL-1 and TNF likely has uses in treating diseases other than septic shock. Use of neutralizing antibodies to TNF or to IL-1 receptors have reduced the consequences of infection and inflammation, including lethal outcomes in animal models. The IL-1 receptor antagonist, a natural-occurring cytokine, blocks shock and death due to Escherichia coli and ameliorates a variety of inflammatory diseases. Soluble TNF and IL-1 surface receptors, which bind their respective cytokines, also ameliorate disease processes. Current clinical trials are evaluating the safety and efficacy of these anticytokine therapies either alone or together.

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Citations
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Journal ArticleDOI

Regulation of the Hypothalamic-Pituitary-Adrenal Axis by Cytokines: Actions and Mechanisms of Action

TL;DR: Findings are reviewed that have documented which cytokines have been shown to influence hormone secretion from the HPA axis, determined under what physiological/pathophysiological circumstances endogenous cytokines regulate HPAaxis activity, established the possible sites of cytokine action on HPA Axis hormone secretion, and identified the potential neuroanatomic and pharmacological mechanisms by which cytokine signal the neuroendocrine hypothalamus.
Journal ArticleDOI

MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia

TL;DR: Macrophage migration inhibitory factor (MIF) is identified as a major secreted protein released by anterior pituitary cells in response to LPS stimulation, and it is concluded that MIF plays a central role in the toxic response to endotoxaemia and possibly septic shock.
Journal ArticleDOI

Management of fever in patients with cancer and treatment-induced neutropenia.

TL;DR: The importance of neutropenia in the risk of serious infection in patients with cancer who are receiving cytotoxic chemotherapy and those with bone marrow failure or human immunodeficiency virus (HIV) infection was first recognized nearly 30 years ago.
Journal ArticleDOI

The pivotal role of tumour necrosis factor α in the development of inflammatory hyperalgesia

TL;DR: Results show that TNFα has an early and crucial role in the development of inflammatory hyperaglesia and the finding that the production of these cytokines is inhibited by steroidal anti‐inflammatory drugs provides a mechanism of action for these drugs in the treatment ofinflammatory hyperalgesia.
References
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Journal ArticleDOI

Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia

TL;DR: Protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion, indicating that cachectin is a mediator of fatal bacteraemic shock and suggesting that antibodies against Cachectin offer a potential therapy of life-threatening infection.
Journal ArticleDOI

Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin

TL;DR: The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin, and this effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin.
Journal ArticleDOI

Detection of circulating tumor necrosis factor after endotoxin administration.

TL;DR: It is concluded that the response to endotoxin is associated with a brief pulse of circulating tumor necrosis factor and that the resultant responses are effected through the cyclooxygenase pathway.
Journal ArticleDOI

Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI.

TL;DR: The predicted protein sequence shows extensive homology with an uncharacterized open reading frame, BCRFI, in the Epstein-Barr virus genome, suggesting the possibility that this herpes virus exploits the biological activity of a captured cytokine gene to enhance its survival in the host.
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