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-γ is key to brucella resistance, contrary to expectations, we found that ex vivo splenocytes from naïve BALB/c mice produced IL-12 and interferon-γ in cultures with brucellae at levels comparable to those of splenocytes from the more resistant C57BL/10 mice. Moreover, both IL-12 and interferon-γ were produced in the first week following infection of BALB/c mice. However, by the third week of infection we found decreased IL-12Rβ2 expression by BABL/c splenocytes, corresponding to their inability to produce interferon-γ in Brucella recall responses at this time as reported previously. Administering recombinant IL-12 to these mice ameliorated the interferon-γ hiatus, resulted in a 1000-fold reduction in CFU during primary infection and increased survival following secondary challenge.