LEISHMANIA MAJOR-INFECTED C3H MICE TREATED WITH ANTI-IL-12 MAB DEVELOP BUT DO NOT MAINTAIN A TH2 RESPONSE

Leishmania major-infected C3H mice develop a Th1 response, but studies have shown that treatment of C3H mice with anti-IL-12 or anti-IFN-gam ma mAb promotes the development of a Th2 response and susceptibility. However, we discovered that C3H mice treated for 3 wk with either anti -IL-12 or anti-IFN-gamma mAb eventually resolved their lesions and swi tched from a Th2 to a Th1 response. No significant differences in IL-4 , IL-10, or IFN-gamma levels or in the parasite burden could be detect ed between BALB/c and anti-IL-12-treated C3H mice early after infectio n, suggesting that the instability of the Th2 response in anti-IL-12-t reated C3H mice was unrelated to levels of these cytokines and parasit e numbers. However, anti-IL-12-treated C3H mice continued to produce I L-12 in spite of exhibiting a Th2 phenotype. To determine whether the production of IL-12 was associated with the healing observed in these animals, we treated C3H mice with anti-IL-12 continuously for 12 wk. I n contrast to C3H mice given anti-IL-12 for 3 wk, C3H mice continuousl y treated with anti-IL-12 failed to heal. These results suggest that q ualitative differences in Th2-type responses may influence their stabi lity and that the presence of IL-4, IL-10, or high parasite numbers is not sufficient to maintain a Th2 response in mice with certain geneti c backgrounds.