RECOMBINANT INTERLEUKIN-12 ENHANCES RESISTANCE OF MICE TO LISTERIA-MONOCYTOGENES INFECTION

The effect of recombinant murine IL-12 (rIL-12) or anti-IL-12 antibody administration on resistance to murine listeriosis was investigated. Mice given a single 0.5 mu g dose of rIL-12 had 1.5 log(10) fewer list eriae in their spleens and livers as compared with control infected mi ce 3 days after L. monocytogenes challenge. Conversely, administration of anti-IL-12 IgG caused an equivalent increase in the cfu of L. mono cytogenes recovered from the spleens and livers as compared to control mice. This is the first report of such a protective effect from a sin gle dose of rIL-12. Treatment of uninfected mice with rIL-12 induced I FN-gamma mRNA production in their livers. Infection of mice with L. mo nocytogenes caused a similar increase in IFN-gamma mRNA levels that wa s not increased further by concurrent treatment with rIL-12. Treatment of mice with an anti-IFN-gamma MAb eliminated the protective effect o f IL-12 on Listeria infection. Expression of TNF-alpha, IL-10 and IL-1 2p40 mRNA in L. monocytogenes-infected mice were not significantly alt ered by administration of either anti-IL-12 IgG or rIL-12. rIL-12 admi nistration was associated with increased serum AST levels, a measure o f liver damage, 1 day after treatment in L. monocytogenes-infected mic e. In addition, rIL-12 administration was associated with the increase d presence of small inflammatory foci and necrotic hepatocytes in both infected and uninfected mice, suggesting a proinflammatory role for I L-12 in the liver.