The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin.
Open accessAbstract
Tumor necrosis factors (TNF) alpha and beta are structurally related cytokines that mediate a wide range of immunological, inflammatory, and cytotoxic effects. During bacterial infection of the bloodstream (sepsis), TNF-alpha induction by bacterial endotoxin is thought to be a major factor contributing to the cardiovascular collapse and critical organ failure that can develop. Despite antibiotic therapy, these consequences of sepsis continue to have a high mortality rate in humans. Here we describe a potent TNF antagonist, a TNF receptor (TNFR) immunoadhesin, constructed by gene fusion of the extracellular portion of human type 1 TNFR with the constant domains of human IgG heavy chain (TNFR-IgG). When expressed in transfected human cells, TNFR-IgG is secreted as a disulfide-bonded homodimer. Purified TNFR-IgG binds to both TNF-alpha and TNF-beta and exhibits 6- to 8-fold higher affinity for TNF-alpha than cell surface or soluble TNF receptors. In vitro, TNFR-IgG blocks completely the cytolytic effect of TNF-alpha or TNF-beta on actinomycin D-treated cells and is markedly more efficient than soluble TNFR (24-fold) or monoclonal anti-TNF-alpha antibodies (4-fold) in inhibiting TNF-alpha. In vitro, TNFR-IgG prevents endotoxin-induced lethality in mice when given 0.5 hr prior to endotoxin and provides significant protection when given up to 1 hr after endotoxin challenge. These results confirm the importance of TNF-alpha in the pathogenesis of septic shock and suggest a clinical potential for TNFR-IgG as a preventive and therapeutic treatment in sepsis.
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Cites
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A. (1987) · Nature · doi:10.1038/330662a0 · Cited by 2,448
Detection of circulating tumor necrosis factor after endotoxin administration
Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182301 · Cited by 1,677
Cited by
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Pfeffer, K., Matsuyama, T., Kündig, T. M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P. S., Krönke, M., & Mak, T. W. (1993) · Cell · doi:10.1016/0092-8674(93)90134-c · Cited by 1,677
Tumor necrosis factor: a pleiotropic cytokine and therapuetic target
Tracey, M. D., & Cerami, P. D. (1994) · Annual Review of Medicine · doi:10.1146/annurev.med.45.1.491 · Cited by 1,063
Tilg, H., Trehu, E., Atkins, M., Dinarello, C., & Mier, J. (1994) · Blood · doi:10.1182/blood.v83.1.113.113 · Cited by 817
Yano, K., Tsuda, E., Washida, N., Kobayashi, F., Goto, M., Harada, A., Ikeda, K., Higashio, K., & Yamada, Y. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.4.518 · Cited by 363
Metadata
- Authors
- Ashkenazi, A., Marsters, S. A., Capon, D. J., Chamow, S. M., Figari, I. S., Pennica, D., Goeddel, D. V., Palladino, M. A., & Smith, D. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1991-12
- Volume
- 88
- Issue
- 23
- Pages
- 10535-10539
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2022522156
- Cited by
- 275
- References
- 2
- FWCI
- 19.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Ashkenazi, A., Marsters, S. A., Capon, D. J., Chamow, S. M., Figari, I. S., Pennica, D., Goeddel, D. V., Palladino, M. A., & Smith, D. H. (1991). Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.88.23.10535
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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