Treatment of Brucella-susceptible mice with IL-12 increases primary and secondary immunity.

Brucella spp. cause disease in humans and livestock and are potential biowarfare agents. Defining the protective immune response is necessary to design vaccines. This has largely been done with mice, brucella-susceptible BALB/c and resistant C57BL strains. Since interferon-gamma is key to brucella resistance, contrary to expectations, we found that ex vivo splenocytes from naïve BALB/c mice produced IL-12 and interferon-gamma in cultures with brucellae at levels comparable to those of splenocytes from the more resistant C57BL/10 mice. Moreover, both IL-12 and interferon-gamma were produced in the first week following infection of BALB/c mice. However, by the third week of infection we found decreased IL-12Rbeta2 expression by BABL/c splenocytes, corresponding to their inability to produce interferon-gamma in Brucella recall responses at this time as reported previously. Administering recombinant IL-12 to these mice ameliorated the interferon-gamma hiatus, resulted in a 1000-fold reduction in CFU during primary infection and increased survival following secondary challenge.

Hyperbaric oxygen inhibits benign and malignant human mammary epithelial cell proliferation.

BACKGROUND: Hyperbaric oxygenation (HBO) therapy is the administration of 100%-inhaled oxygen to patients at increased atmospheric pressure. MATERIALS AND METHODS: We used an in vitro model to examine the effects of HBO on mammary cell proliferation. Normal mammary epithelia, primary tumor and metastatic tumor cells derived from the same patient and immortalized by transfection with the human papilloma virus E6 oncogene, as well as the MCF7 human mammary adenocarcinoma cell line, were studied. RESULTS: HBO (97.9% O2, 2.1% CO2, 2.4 atmospheres absolute) inhibited the proliferation of all 4 cell types as measured by light microscopy, [3H]thymidine uptake, a tetrazolium-based colorimetric assay and a clonogenicity assay. The anti-proliferative effect of HBO was time-dependent (p < 0.01 for all 4 cell types). Hyperoxia alone (95% O2, 5% CO2, 1 atmosphere absolute) and increased atmospheric pressure alone (8.75% O2, 2.1% CO2, 2.4 atmospheres absolute) also inhibited proliferation, but their effects were not as profound as HBO (p < 0.01 when either hyperoxia or increased pressure was compared to HBO for all 4 cell types). HBO enhanced the anti-proliferative effects of melphalan (p < 0.05), gemcitabine (p < 0.001) and paclitaxel (p < 0.001). The clonogenicity assay demonstrated that the effects of HBO were still evident 2 weeks after the exposure (p < 0.01 for all 4 cell types). Experiments using Hoechst-propidium iodide or annexin V-propidium iodide staining showed no HBO-induced increases in necrosis or apoptosis. CONCLUSION: HBO inhibits benign and malignant mammary epithelial cell proliferation, but does not enhance cell death.