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Limited involvement of interleukin-6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin-6 or its receptor in various murine models

(1992) EUROPEAN JOURNAL OF IMMUNOLOGY. 22(10). p.2625-2630
Author
Organization
Abstract
Several studies in human patients and in laboratory animals have revealed a correlation between serum interleukin (IL)-6 levels and outcome in clinical sepsis and in related animal models, respectively. In the present study, two monoclonal antibodies were used to investigate the contribution of IL-6 in the lethal action of tumor necrosis factor (TNF) and of lipopolysaccharide (LPS) in mice.We studied the potential protective properties of an anti-murine (m) IL-6 antibody and of an anti-mIL-6 receptor antibody. In controlled experiments, we observed that both monoclonal antibodies conferred a dose-dependent protection to a lethal dose of mTNF. Detailed studies with the monoclonal antibodies indicate, however, that protection was no longer observed when the mTNF dose was slightly higher than the lethal dose. Likewise, the anti-IL-6 monoclonal antibody protected against injections of LPS at a lethal-dose concentration, but here too failed to protect against higher doses of LPS. The anti-IL-6 monoclonal antibody was unable to protect against mTNF in mice sensitized by galactosamine, the corticoid receptor antagonist RU38486 or human (h) IL-1beta. Protection did not correlate with the serum concentrations of IL-6. Finally, we demonstrate that hIL-6 injection did not change the sensitivity of mice towards mTNF. We conclude that, although IL-6 levels may be of value as a marker for the outcome in septic shock, this cytokine contributes only marginally in the pathogenesis leading to death. The small, but real, contribution of IL-6 in some situations might be due to its ability to up-regulate the level of TNF receptors.
Keywords
MICE, TUMOR-NECROSIS-FACTOR, INVIVO, LIPOPOLYSACCHARIDE, ANTAGONIST, CACHECTIN, ENDOTOXIN, PROTECT, CELLS

Citation

Please use this url to cite or link to this publication:

MLA
Libert, Claude, Anne Vink, Pierre Coulie, et al. “Limited Involvement of Interleukin-6 in the Pathogenesis of Lethal Septic Shock as Revealed by the Effect of Monoclonal Antibodies Against Interleukin-6 or Its Receptor in Various Murine Models.” EUROPEAN JOURNAL OF IMMUNOLOGY 22.10 (1992): 2625–2630. Print.
APA
Libert, C., Vink, A., Coulie, P., Brouckaert, P., Everaerdt, B., Van Snick, J., & Fiers, W. (1992). Limited involvement of interleukin-6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin-6 or its receptor in various murine models. EUROPEAN JOURNAL OF IMMUNOLOGY, 22(10), 2625–2630.
Chicago author-date
Libert, Claude, Anne Vink, Pierre Coulie, Peter Brouckaert, Bart Everaerdt, Jacques Van Snick, and Walter Fiers. 1992. “Limited Involvement of Interleukin-6 in the Pathogenesis of Lethal Septic Shock as Revealed by the Effect of Monoclonal Antibodies Against Interleukin-6 or Its Receptor in Various Murine Models.” European Journal of Immunology 22 (10): 2625–2630.
Chicago author-date (all authors)
Libert, Claude, Anne Vink, Pierre Coulie, Peter Brouckaert, Bart Everaerdt, Jacques Van Snick, and Walter Fiers. 1992. “Limited Involvement of Interleukin-6 in the Pathogenesis of Lethal Septic Shock as Revealed by the Effect of Monoclonal Antibodies Against Interleukin-6 or Its Receptor in Various Murine Models.” European Journal of Immunology 22 (10): 2625–2630.
Vancouver
1.
Libert C, Vink A, Coulie P, Brouckaert P, Everaerdt B, Van Snick J, et al. Limited involvement of interleukin-6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin-6 or its receptor in various murine models. EUROPEAN JOURNAL OF IMMUNOLOGY. 1992;22(10):2625–30.
IEEE
[1]
C. Libert et al., “Limited involvement of interleukin-6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin-6 or its receptor in various murine models,” EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 22, no. 10, pp. 2625–2630, 1992.
@article{207116,
  abstract     = {Several studies in human patients and in laboratory animals have revealed a correlation between serum interleukin (IL)-6 levels and outcome in clinical sepsis and in related animal models, respectively. In the present study, two monoclonal antibodies were used to investigate the contribution of IL-6 in the lethal action of tumor necrosis factor (TNF) and of lipopolysaccharide (LPS) in mice.We studied the potential protective properties of an anti-murine (m) IL-6 antibody and of an anti-mIL-6 receptor antibody. In controlled experiments, we observed that both monoclonal antibodies conferred a dose-dependent protection to a lethal dose of mTNF. Detailed studies with the monoclonal antibodies indicate, however, that protection was no longer observed when the mTNF dose was slightly higher than the lethal dose. Likewise, the anti-IL-6 monoclonal antibody protected against injections of LPS at a lethal-dose concentration, but here too failed to protect against higher doses of LPS. The anti-IL-6 monoclonal antibody was unable to protect against mTNF in mice sensitized by galactosamine, the corticoid receptor antagonist RU38486 or human (h) IL-1beta. Protection did not correlate with the serum concentrations of IL-6. Finally, we demonstrate that hIL-6 injection did not change the sensitivity of mice towards mTNF. We conclude that, although IL-6 levels may be of value as a marker for the outcome in septic shock, this cytokine contributes only marginally in the pathogenesis leading to death. The small, but real, contribution of IL-6 in some situations might be due to its ability to up-regulate the level of TNF receptors.},
  author       = {Libert, Claude and Vink, Anne and Coulie, Pierre and Brouckaert, Peter and Everaerdt, Bart and Van Snick, Jacques and Fiers, Walter},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keywords     = {MICE,TUMOR-NECROSIS-FACTOR,INVIVO,LIPOPOLYSACCHARIDE,ANTAGONIST,CACHECTIN,ENDOTOXIN,PROTECT,CELLS},
  language     = {eng},
  number       = {10},
  pages        = {2625--2630},
  title        = {Limited involvement of interleukin-6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin-6 or its receptor in various murine models},
  url          = {http://dx.doi.org/10.1002/eji.1830221023},
  volume       = {22},
  year         = {1992},
}

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