ENHANCEMENT BY RECOMBINANT HUMAN INTERLEUKIN-2 OF HOST-RESISTANCE TO TOXOPLASMA-GONDII INFECTION IN PREGNANT MICE

The lymphokine production by pregnant mice infected with a lethal dose of Toxoplasma gondii was evaluated in comparison with that by virgin mice infected with a sublethal dose of this protozoan parasite. Spleno cytes taken from mice before and on the day after infection produced c onsiderable amounts of IL-2 in response to concanavalin A (Con A) stim ulation, but the titers rapidly declined in both pregnant and virgin m ice as infection progressed. A trace amount or undetectable level of I L-2 was produced by splenocytes from acutely infected mice when stimul ated with Toxoplasma lysate antigen (TLA). In contrast to the kinetics of IL-2 production, the levels of IFN-gamma produced by splenocytes c ultured with Con A or TLA increased steadily in the later stage of inf ection in both pregnant and virgin mice. Thus, the response to Con A o r TLA of splenocytes to produce IL-2 and IFN-gamma differed strikingly in acute toxoplasmosis in mice. The administration of rHuIL-2 resulte d in a significant decrease in the mortality of pregnant mice infected with a lethal dose of Toxoplasma. The combination of rHuIL-2 and rMuI FN-gamma increased the survival rate slightly but not significantly co mpared with pregnant mice receiving either rHuIL-2 or rMuIFN-gamma. Mo reover, exogenously administered rHuIL-2 enhanced the production of bo th IFN-alpha and IFN-gamma in the bloodstreams of pregnant mice, in ac cordance with the decreased mortality. These results indicate that IL- 2 may play a significant role in modulating the host defense against T oxoplasma infection in pregnant mice.