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Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice.
Abstract
Potentially fatal physiologic and metabolic derangements can occur in response to bacterial infection in animals and man. Recently it has been shown that alterations in the levels of circulating cytokines such as IL-6 and TNF-alpha occur shortly after bacterial challenge. To understand better the role of IL-6 in inflammation, we investigated the effects of in vivo anti-mouse IL-6 antibody treatment in a mouse model of septic shock. Rat anti-mouse IL-6 neutralizing mAb was produced from splenocytes of an animal immunized with mouse rIL-6. This mAb, MP5-20F3, was a very potent and specific antagonist of mouse IL-6 in vitro bioactivity, demonstrated using the NFS60 myelomonocytic and KD83 plasmacytoma target cell lines, and also immunoprecipitated radiolabeled IL-6. Anti-IL-6 mAb pretreatment of mice subsequently challenged with lethal doses of i.p. Escherichia coli or i.v. TNF-alpha protected mice from death caused by these treatments. Pretreatment of E. coli-challenged mice with anti-IL-6 led to an increase in serum TNF bioactivity, in comparison to isotype control antibody, implicating IL-6 as a negative modulator of TNF in vivo. Anti-TNF-alpha treatment of mice challenged i.p. with live E. coli resulted in a 70% decrease in serum IL-6 levels, determined by immunoenzymetric assay, compared to control antibody, thereby supporting a role for TNF-alpha as a positive regulator of IL-6 levels. We conclude that IL-6 is a mediator in lethal E. coli infection, and suggest that antagonists of IL-6 may be beneficial therapeutically in life-threatening bacterial infection.
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Cited by
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
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Sampson, H. A., Mendelson, L., & Rosen, J. P. (1992) · New England Journal of Medicine · doi:10.1056/nejm199208063270603 · Cited by 1,609
Mizuhara, H., O'Neill, E., Seki, N., Ogawa, T., Kusunoki, C., Otsuka, K., Satoh, S., Niwa, M., Senoh, H., & Fujiwara, H. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.5.1529 · Cited by 517
Guidotti, L. G., Ando, K., Hobbs, M. V., Ishikawa, T., Runkel, L., Schreiber, R. D., & Chisari, F. V. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3764 · Cited by 412
Metadata
- Authors
- Starnes, H. F., Pearce, M. K., Tewari, A., Yim, J. H., Zou, J. C., & Abrams, J. S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1990-12
- Volume
- 145
- Issue
- 12
- Pages
- 4185-4191
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1658552097
- Cited by
- 322
- References
- 0
- FWCI
- 18.85
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- closed
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- CoChat. (2026). Citation check: Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. https://app.cochat.ai/papers/10.4049/jimmunol.145.12.4185
- The paper
- Starnes, H. F., Pearce, M. K., Tewari, A., Yim, J. H., Zou, J. C., & Abrams, J. S. (1990). Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. The Journal of Immunology. https://doi.org/10.4049/jimmunol.145.12.4185
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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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