Journal ArticleDOI
Shock and tissue injury induced by recombinant human cachectin.
Kevin J. Tracey,Bruce Beutler,Stephen F. Lowry,James P Merryweather,Stephen D. Wolpe,Ian W. Milsark,Robert J. Hariri,Thomas J. Fahey,Alejandro Zentella,J. D. Albert,G. Tom Shires,Anthony Cerami +11 more
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TLDR
It appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.Abstract:
Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.read more
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Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Lyudmila V. Borovikova,Svetlana Ivanova,Minghuang Zhang,Huan Yang,Galina I. Botchkina,Linda R. Watkins,Haichao Wang,Naji N. Abumrad,John W. Eaton,Kevin J. Tracey +9 more
TL;DR: Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.
Journal ArticleDOI
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice
Haichao Wang,Ona Bloom,Minghuang Zhang,Jaideep M. Vishnubhakat,Michael Ombrellino,Jiantu Che,Asia Frazier,Huan Yang,Svetlana Ivanova,Lyudmila V. Borovikova,Kirk R. Manogue,Eugen Faist,Edward Abraham,Jan Andersson,Ulf Andersson,Patricia E. Molina,Naji N. Abumrad,Andrew E. Sama,Kevin J. Tracey +18 more
TL;DR: High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1, and showed increased serum levels after endotoxin exposure, suggesting that this protein warrants investigation as a therapeutic target.
Journal ArticleDOI
The inflammatory reflex
TL;DR: The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded understanding of how the nervous system modulates immune responses, and the opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
Journal ArticleDOI
Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease
Marcia M. Shull,Ilona Ormsby,Ann B. Kier,Sharon A. Pawlowski,Ronald J. Diebold,Moying Yin,Ruth D. Allen,Charles L. Sidman,Gabriele Proetzel,Dawn Calvin,Nikki Annunziata,Thomas Doetschman +11 more
TL;DR: TGF-β1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
Journal ArticleDOI
Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.
Hong Wang,Man Yu,Mahendar Ochani,C A Amella,Mahira Tanovic,Seenu Susarla,Jianhua Li,Haichao Wang,Huan Yang,Luis Ulloa,Yousef Al-Abed,Christopher J. Czura,Kevin J. Tracey +12 more
TL;DR: It is reported that the nicotinic acetylcholine receptor α7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.
References
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Journal ArticleDOI
An endotoxin-induced serum factor that causes necrosis of tumors
TL;DR: It is proposed that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.
Journal ArticleDOI
Observations on the Systemic Administration of Autologous Lymphokine-Activated Killer Cells and Recombinant Interleukin-2 to Patients with Metastatic Cancer
Steven A. Rosenberg,Michael T. Lotze,Linda M. Muul,Susan F. Leitman,Alfred E. Chang,S. E. Ettinghausen,Yvedt L. Matory,John M. Skibber,Eitan Shiloni,John T. Vetto,Claudia A. Seipp,Colleen Simpson,Cheryl M. Reichert +12 more
TL;DR: Preliminary results of the systemic administration of autologous lymphokine-activated killer (LAK) cells and the recombinant-derived lymphokin interleukin-2 to patients with advanced cancer are described, based on animal models in which this regimen mediated the regression of established pulmonary and hepatic metastases from a variety of murine tumors in several strains of mice.
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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
Cachectin and tumour necrosis factor as two sides of the same biological coin
Bruce Beutler,Anthony Cerami +1 more
TL;DR: The identity of cachectin and tumour necrosis factor has led to a new view of its therapeutic potential and its ability to induce wasting as well as a lethal state of shock.
Journal ArticleDOI
Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1
Charles A. Dinarello,Joseph G. Cannon,Sheldon M. Wolff,H A Bernheim,Bruce Beutler,Anthony Cerami,Irene S. Figari,Michael A. Palladino,O'connor John +8 more
TL;DR: These studies show that TNF (cachectin) is another endogenous pyrogen which, like IL-1 and IFN-alpha, directly stimulate hypothalamic PGE2 synthesis and is an endogenous inducer ofIL-1.