COMPARISON OF T-CELL CYTOKINES IN RESISTANT AND SUSCEPTIBLE MICE INFECTED WITH VIRULENT BRUCELLA-ABORTUS STRAIN-2308

C57BL/10 and BALB/c mice differ in their abilities to clear infections with the intracellular bacterium Brucella abortus strain 2308. We hav e previously reported that in vivo neutralization of IL-10 in the susc eptible BALB/c mice results in significantly fewer bacteria in their s pleens 1 week after infection with 5 x 10(3) colony forming units (CFU ) of 2308. Here we extend those studies and report a similar effect wh en IL-4 is neutralized. In contrast, in the more resistant C57BL/10 mi ce infected with 5 x 10(3) CFU, neither neutralization of IL-10 nor IL -4 significantly decreased the level of infection nor did it in either BALB/c or C57BL/10 mice infected with a 1000-fold higher dose of stra in 2308. While splenocytes from the later mentioned groups of mice pro duced IL-10 in response to stimulation with brucella antigen, they als o produced higher levels of interferon (IFN)-gamma than those from BAL B/c mice infected with the low challenge dose of 5 x 10(3) CFU. Result s of in vivo neutralization of IFN-gamma by monoclonal antibodies (MAb ) reported here and elsewhere indicated that IFN-gamma, is important f or control; thus, we postulate that the higher levels of IFN-gamma may override the detrimental effects of Th2 cytokines. In vitro studies a lso showed that macrophages from the more resistant C57BL/10 mice were less susceptible to the ability of IL-10 to decrease anti-brucella ac tivities than were BALB/c macrophages. CD4(+) T cells were principally responsible for the production of IL-10 in BALB/c but not C57BL/10 sp lenocyte populations. C57BL/10 splenocytes produced more IFN-gamma tha n those from BALB/c mice in response to stimulation with brucella anti gens. These differences between BALB/c and C57BL/10 mice may contribut e to the superior capacity of C57BL/10 mice to control infections with B. abortus strain 2308.