Opposing roles for interferon regulatory factor-3 (IRF-3) and type I interferon signaling during plague.

Type I interferons (IFN-I) broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs) following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-ß was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-ß following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-ß signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-ß production.

Evaluation of lomustine as a rescue agent for cats with resistant lymphoma.

This retrospective study evaluated the use of lomustine as a rescue agent for 39 cases of resistant feline lymphoma. Parameters assessed included lymphocyte cell size, number of previous chemotherapy drugs and number of previous chemotherapy protocols received, time from lymphoma diagnosis to initiation of lomustine therapy, body weight and anatomic location of lymphoma. Cell size, number of previous chemotherapy drugs, number of previous chemotherapy protocols and anatomic location were all significant prognostic factors for the progression-free interval. Twenty-one cats (54%) received more than one dose of lomustine. The overall median progression-free interval (MPFI) was 39 days (range 7-708 days). The MPFI for large versus small and intermediate cell lymphomas was 21 versus 169 days, respectively. The MPFI for gastrointestinal versus non-gastrointestinal lymphomas was 180 versus 25.5 days, respectively. Lomustine has an acceptable efficacy and safety for use as a rescue agent in feline lymphoma.