**5. Conclusions**

In the past few years circulating cf-DNA has been identified as a prognostic marker in severe sepsis [11,48,49]. Indeed cf-DNA was shown to have better discriminatory power than IL-6, thrombin or protein C to predict ICU mortality in sepsis [11]. The cellular origin of cf-DNA from host cells was shown by Dwivedi *et al.* [11] who confirmed that the release of cf-DNA was independent of the infecting organism and was likely mediated by inflammatory mediators generated during the exacerbated host immune response. Our study showed attenuated NET formation and reduced cf-DNA in the serum of septic VitC sufficient mice and in VitC deficient mice treated with ascorbic acid (Figure 1). Our study did not examine the origin of cf-DNA in the serum of these mice. It is possible that some of this DNA could be non-neutrophilic in origin since mast cells, eosinophils, and basophils have also been shown to expel their DNA in a manner similar to PMNs [50]. However, a detailed examination of the origin of cf-DNA in these septic mice is beyond the scope of this study. Nevertheless, data from our study implies that attenuation of NETs maybe crucial for resolution of sepsis in mice.

Overall, our *in vitro* and *in vivo* findings identify a novel regulatory mechanism that limits NET formation in sepsis. These findings implicate VitC as a previously unrecognized layer of regulation that prevents generation of excessive NETs.
