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Resistance to murine leishmaniasis correlates with development of a [CD4.sup.+] T helper 1 (Th1)-predominant immune response. To determine whether immunostimulatory CpG-containing oligodeoxynucleotides (CpG-ODN), known to promote a Th1 immune response, could provide protection from Leishmania infection, CpG-ODN and freeze-thawed (F/T) Leishmania major were coinjected intradermally into susceptible BALB/c mice. A Leishmania-specific Th1-predominant immune response was induced, and 40% of animals were protected from subsequent challenge with infectious organisms, with 0% protection of animals injected with F/T Leishmania organisms and PBS, F/T organisms and control ODN, or F/T organisms alone. More striking protection (65-95%) was seen in mice first infected with intact Leishmania organisms and then injected with CpG-ODN, either at the site of infection or at a remote site. To determine whether the therapeutic protection provided by CpG-ODN depended on IL-12 and IFN-[Gamma] production, both IFN-[Gamma]-deficient BALB/c mice and BALB/c mice treated with neutralizing anti-IL-12 mAb were first inoculated with Leishmania and then treated with either CpG-ODN, ODN, or PBS. None of these IFN-[Gamma]-deficient mice survived (0/20, 0/20, and 0/20 respectively). Furthermore, neutralization of IL-12 completely abolished the therapeutic protection provided by CpG-ODN (0/20 mice surviving). We conclude that immunostimulatory DNA sequences likely exert systemic effects via IL-12 and IFN-[Gamma]-dependent mechanisms and hold considerable promise as both vaccine adjuvants and potential therapeutic agents in the prevention and treatment of leishmaniasis.

IgE-IC helps in intracellular killing of L. major in human monocyte-derived macrophages by the induction of the L-arginine: NO pathway, which is revealed by increased generation of nitrite (NO2 negative), the stable oxidation product of NO, and by the ability of N (super G)-monomethyl-L-arginine to block NO generation and as well as parasite killing. Similarly NO-dependent effect is seen with interferon gamma-treated cells due to tumour necrosis factor alpha as both the induction of NO synthase and the killing of parasites.

A combination of interleukin 12 (IL-12) and the antimony-based leishmanicidal drug Pentostam is used to treat Leishmania major infected mice. This treatment is connected to a switch from a type 2 to a type 1 T helper (Th2 and Th1) cell response. When the levels of antigen are diminished the IL-12 appears to restrain a Th2 response and activate a Th1 response.