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Kell Malcolm R.; Kavanagh, Eamon G.; Goebel, Andreas; Soberg, Christopher C.; Lederer, James A.


We previously reported the high lethality of CD4+ T-cell activation in burn-injured T-cell receptor (TCR) transgenic mice. This suggested to us that T-cells may play a role in the development of the systemic inflammatory response syndrome (SIRS) which can occur after severe injury. In this study, we sought a more clinically relevant model to test the hypothesis that naturally produced bacterial toxins that are known to act as potent polyclonal T-cell activating agents may induce a similar lethal shock-like response in injured, non-TCR transgenic mice. Accordingly, sham- or burn-injured mice were treated with various doses of staphylococcal enterotoxin A (SEA), then observed for 48-hour mortality. We observed 94% and 56% 48-h mortality when burn-injured mice were given 15 μg and 10 μg of SEA, respectively, while neither SEA dose caused mortality in sham-injured mice. The assessment of serum cytokine levels demonstrated significantly elevated interleukin 2 (IL-2) and tumor necrosis factor α (TNFα) levels when compared to sham mice (P < 0.01). In vitro studies confirmed our in vivo results and also demonstrated elevated levels of interferon γ (IFNγ) (P < 0.01). We also observed a novel injury-dependent switch from CD4+ to CD8+ T-cells as the dominant T-cell type producing TNFα and IFNγ in response to SEA stimulation in vitro. Taken together, our findings indicate that injury primes the immune system for an augmented early T-cell response that can result in a lethal shock-like syndrome.

©1999The Shock Society