Background. Recent findings indicate that severe injury primes the immune s
ystem for nn enhanced and lethal proinflammatory cytokine response against
bacterial-derived superantigens. This study asked whether this response to
injury involves the CD95 (Fas) signaling pathway.
Methods. To assess superantigen-mediated mortality wild-type (WT) C57BL/6 a
nd Fns-deficient C57BL/6 lpr (-/-) (lpr) mice underwent burn or sham injury
and were challenged 2 hours later with staphylococcal enterotoxin B (SEB).
Spleen cells from sham and burn WT or lpr mice were stimulated in vitro wi
th SEE to assess injury effects on IL-2 TNF-alpha, and IFN-gamma production
.
Results. Lpr burn mice survived the SEB challenge (100% survival), while WT
burn mice showed a high mortality (17% survival, P <001, analysis of varia
nce [ANOVA]). Sham lpr or WT mice suffered no mortality to the SEE challeng
e. In vitro studies demonstrated that burn lpr mice produced significantly
less TNF-alpha, IFN-gamma, IL-2 than burn WT mice (P <.01, ANOVA. Burn inju
ry markedly enhanced SEB-stimulated IFN-gamma production by WT spleen cells
and CD8+ T cells, while this did not occur in SEB-stimulated lpr spleen ce
lls.
Conclusions. These findings support the hypothesis that the CD95 (Fas) sign
aling pathway plays an integral role in the injury-induced enhanced and let
hal T-cell reactivity against bacterial superantigens.