In our studies we found that VSV induced robust production of IL-1b in vivo and that IL-1b was still produced in mice lacking caspase-1 or ASC. One caveat to those findings is that ELISA assays such as the one used here do not rigorously discriminate between detection of pro-IL-1b and detection of the cleaved active IL-1b. Therefore it is possible that the some of the IL-1b detected in caspase2/2 mice was not biologically active. Precise determination of the amount of active IL-1b present in caspase2/2 mice will require the development of better detection reagents. Despite this limitation, our results support a model in which there are multiple pathways by which mature IL-1b is produced in vivo in response to VSV. The data are also consistent with the idea that the manner in which mature IL-1b is produced (via caspase-1 or not) may vary with the cell in which the IL-1b is induced. We further observed that mice lacking caspase-1 or ASC were not protected from acute pathology to the same extent that IL-1R2/ 2 mice were. That meant that VSV vectors engineered to suppress components of the RIG-I/ASC/caspase-1 inflammasome, or the Nlrp3/ASC/caspase-1 inflammasome, would be unlikely to be significantly less reactogenic than the parent vector. On the other hand, rVSV designed to suppress the biological response to IL-1b (for example via inclusion of a soluble IL-1b trap), or to IL-1a and IL-1b (via inclusion of a soluble IL-1 receptor antagonist) might reduce the biological response to IL-1 in vivo and therefore be less reactogenic.