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Mediators of Inflammation
Volume 2010, Article ID 517594, 7 pages
http://dx.doi.org/10.1155/2010/517594
Research Article

Proinflammatory Mediators of Toxic Shock and Their Correlation to Lethality

1Integrated Toxicology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA
2Statistics Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA

Received 20 October 2009; Revised 3 March 2010; Accepted 22 March 2010

Academic Editor: Tânia Fröde

Copyright © 2010 Teresa Krakauer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bacterial exotoxins and endotoxins both stimulate proinflammatory mediators but the contribution of each individual toxin in the release of mediators causing lethal shock is incompletely understood. This study examines the cytokine response and lethality of mice exposed to varying doses of staphylococcal enterotoxin B (SEB) or lipopolysaccharide (LPS) and their combinations. In vivo, SEB alone induced moderate levels of IL-2 and MCP-1 and all mice survived even with a high dose of SEB (100 g/mouse). LPS (80 g/mouse) caused 48% lethality and induced high levels of IL-6 and MCP-1. SEB induced low levels of TNF , IL-1, IFN , MIP-2, and LPS synergized with SEB in the expression of these cytokines and that of IL-6 and MCP-1. Importantly, the synergistic action of SEB and LPS resulted in lethal shock and hypothermia. ANOVA of cytokine levels by survival status of SEB-plus-LPS groups revealed significantly higher levels of TNF , IL-6, MIP-2, and MCP-1 in nonsurvivors measured at 8 hours. Significantly higher levels of IFN and IL-2 were observed at 21 hours in nonsurvivors of toxic shock compared to those in survivors. Overall, synergistic action of SEB and LPS resulted in higher and prolonged levels of these key cytokines leading to toxic shock.