Inflammatory cell differential counts, or gross lung histology. Interestingly, the one difference we identified was that ZFP36 mRNA levels were increased in lavaged macrophages. This finding indicates that ZFP36 may be increased to functionally compensate for the lack of ZFP36L1, supporting the notion that the Zfp36 family members have some overlapping functions. Although, to our knowledge, ZFP36L1 levels have not been measured in the ZFP36 deficient mice it is clear that even if it were increased to compensate for the lack of ZFP36, it is insufficient to limit cytokine over-production and inflammatory damage. Despite the lack of increased cytokines in the lung at baseline in the ZFP36L1 deficient mice, we hypothesized that we would observe a difference in cytokine expression under stimulated conditions such as early after infection. Given that ZFP36L1 is present only in low levels at baseline in alveolar macrophages and is rapidly induced in response to bacteria with a peak expression in vivo between 2 and 6 hours, we measured cytokine levels as well as inflammatory cell recruitment to the lung at early time points after infection. We were surprised to find that there were no detectable differences in select macrophage produced cytokine in the BAL fluid, including TNF-a, which is overproduced in the absence of myeloid ZFP36. There was also no alteration in differential leukocyte counts at baseline or at 3 hours after infection, and the two OTX015 groups had similar neutrophil recruitment demonstrated after 6 hours of infection. Consistent with this finding, we also did not detect any differences in select cytokine production in cultured murine alveolar macrophages 6 hours after stimulation with E. coli or LPS. Of note, measurements of ZFP36 mRNA 3 hours after infection were no longer different between the groups. While these findings were surprising, we acknowledge that measurements at isolated time points after infection are limited in their ability to detect alterations in such a dynamic and rapidly-changing response. Given the limitations of measurements and isolated time points, to best determine whether myeloid ZFP36L1 is important for the inflammatory response of the lung and for maintaining the balance between sufficient inflammation to prevent pneumonia but not enough to cause excessive lung injury, we next evaluated outcomes of pneumonia at longer time points. Contrary to our hypothesis, we found no differences in markers of bacterial clearance, severity of illness or lung injury in either a gram positive or a gram negative lung infection. Further, there were no differences in these markers after a systemic infection inducing a global sepsis response E. coli. This is particularly notable, as mice with myeloid deficiency of ZFP36 show extreme susceptibility to sepsis induced by LPS. Contrary to our hypothesis, this lack of an innate immune phenotype indicated that either ZFP36L1 does not play a role in an integrated host defense, the presence of ZFP36 and/or ZFP36L2 can compensate for the loss of ZFP36L1 as has been recently shown in T cells, or that ZFP36L1 expression in other innate immune cells outside of the myeloid lineage compensate for macrophage ZFP36L1 deficiency.