Elevated plasma levels of interferon (IFN)-γ, IFN-γ inducing cytokines, and IFN-γ inducible CXC chemokines in visceral leishmaniasis

Interferon (IFN)-gamma plays an important role during immune responses against leishmaniasis. Production of IFN-gamma is regulated by interleukin (IL)-12, IL-18, and IL-15. Interferon-gamma-inducible protein (IP)-10 and monokine induced by IFN-gamma (Mig) are CXC chemokines, the production of which, at least in part, is IFN-gamma dependent. A follow-up study of individuals infected with Leishmania donovani was undertaken in an area of Ethiopia endemic for visceral leishmaniasis (VL). Plasma levels of IFN-gamma, IL-12p40, IL-18, IL-15, IP-10, and Mig were markedly elevated in symptomatic VL patients (n = 70) compared with individuals with asymptomatic Leishmania infections (n = 39), malaria patients (n = 13), and healthy controls from the endemic area (n = 12). A significant decrease of IFN-gamma and all mediators was observed after treatment of VL patients (n = 33). These data show that increased plasma levels of IFN-gamma, as well as the mediators involved in the production and the activity of this cytokine, are characteristic of active VL in humans, and may play an important immunopathogenic role. The data also suggest that in patients with VL, the production of type 1 cytokines is not depressed, but there appears to be an unresponsiveness to the stimuli of type I cytokines. The underlying causes of immunologic unresponsiveness remain a subject of further investigation.