The cell-mediated immune response is critical in the resistance to and
recovery from leishmaniasis. Cytokines are central elements in mounti
ng an immune response and have received a great deal of attention in b
oth human and experimental leishmaniasis. IFN-gamma is responsible for
macrophage activation leading to leishmanicidal mechanisms, Understan
ding the balance of cytokines that lead to enhanced production of or s
ynergize with IFN-gamma, and those cytokines that counterbalance its e
ffects is fundamental for developing rational immunotherapeutic or imm
unoprophylactic approaches to leishmaniasis, Here we focus on the cyto
kine balance in human leishmaniasis, particularly IL-10 as an IFN-gamm
a opposing cytokine, and IL-12 as an IFN-gamma inducer, The effects of
these cytokines were evaluated in terms of several parameters of the
human immune response, IL-10 reduced lymphocyte proliferation, IFN-gam
ma production and cytotoxic activity of responsive human peripheral bl
ood mononuclear cells. Neutralization of IL-10 led to partial restorat
ion of lymphoproliferation, IFN-gamma production and cytotoxic activit
y in unresponsive visceral leishmaniasis patients, IL-12 also restored
the responses of peripheral blood mononuclear cells from visceral lei
shmaniasis patients. The responses obtained with IL-12 are higher than
those obtained with anti-IL-10, even when anti-IL-10 is combined with
anti-IL-4.