Mice deficient in the IL-1R control rVSV replication, have normal cellular and humoral immune responses, and are immune to high dose re-challenge IL-1b causes some deleterious effects such as fever and anorexia, but has also been shown to contribute positively to the generation of adaptive immune responses induced by live virus infection [23] . The role of IL-1 in control of VSV replication has not been examined previously, and reports describing the role of IL-1 in control of other viruses in vivo are not in agreement. Because our ultimate goal is to be able to generate less reactogenic rVSV vectors by attenuating the host inflammatory response, it was important to determine whether IL-1 was required for the control of vaccine vector replication, generation of humoral and cellular immune responses, or to generate protection against rechallenge. To investigate these questions we intramuscularly immunized mice deficient in the IL-1 receptor (IL-1R2/2) with 5610 8 PFU of rVSV and measured viral loads, induction of antibody and T cell responses, and protection from rechallenge. As shown in Figure 3A , viral loads in the quadriceps muscle (injection site) were not significantly different between wild type and IL-1R2/2 mice (n = 3 per group) at 24 hours after infection, which is the peak of VSV replication in vivo. Also, virus was not detected 2) are protected from acute weight loss after intramuscular immunization with rVSV. Eight to ten week old female C57BL/6 mice were immunized with a single intramuscular injection to the left rear quadriceps of 5610 8 PFU of live replicating rVSV. Graph shows average percent initial weight by day for each group of mice beginning on the day of immunization (Day 0). IL-1R2/2 mice (n = 3) lost less weight and recovered more quickly than wild type (WT, n = 4) mice after immunization. The difference in weight loss was significant from day 1-day 4 after challenge (P = 0.03, Mann-Whitney test). This experiment has been performed two times with consistent results. doi:10.1371/journal.pone.0046516.g001