ELEVATED PLASMA LEVELS OF INTERFERON (IFN)-γ, IFN-γ INDUCING CYTOKINES, AND IFN-γ INDUCIBLE CXC CHEMOKINES IN VISCERAL LEISHMANIASIS

Abstract

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 1 cytokines. The underlying causes of immunologic unresponsiveness remain a subject of further investigation.

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

“…The plasma concentrations of most of the analysed cytokines (IFN-γ, TNF-α, IL-4 and IL-10) were higher in the subjects with active VL relative to the other groups, demonstrating an exacerbation of the immune response in these patients; this elevation in cytokine levels is in agreement with results from other studies (Hailu et al 2004, Peruhype-Magalhães et al 2005, Kurkjian et al 2006, Khoshdel et al 2009). Here, a mixed cytokine profile (Th1 and Th2) was detected in the patients with the active disease.…”

“…Additionally, higher concentrations of IFN-γ were detected in the patients with the active disease, which is in agreement with results from other studies (Hailu et al 2004, Caldas et al 2005, Ansari et al 2006. IFN-γ is likely produced in lymphoid organs where Leishmania proliferates (Goto & Prianti 2009).…”

“…The immunological mechanism involved in the infection and the relationship between the immune system and the clinical forms of the disease have been studied by evaluating cellular profiles and cytokine production in bone marrow, spleen and lymph node aspirates, as well as in peripheral blood mononuclear cells and in plasma samples from patients with different clinical forms of VL. Analysis of plasma samples is a suitable alternative to the other methods because it is simpler and less invasive (Hailu et al 2004, Peruhype-Magalhães et al 2005, Khoshdel et al 2009). …”

Splenic immune responses during canine visceral leishmaniasis

“…The involvement of chemokines in leishmaniasis was investigated primarily using murine models of leishmaniasis [13,35,44]. A few studies have examined chemokine responses locally in the skin or peripheral blood mononuclear cells of people with leishmaniasis [20,34]. However, no information is available on the pattern of chemokine expression in visceral organs during HVL or during CVL.…”

Immunoactivation and immunopathogeny during active visceral leishmaniasis

“…Although some studies evaluating cytokines in serum samples have either not detected or found low concentrations of 69,70 , other studies have produced conflicting results. IFN-g was detected in 17 of 44 patients in Iran 2 and in 13 of 15 patients in Brazil 20 ; in addition, high levels have been confirmed in patients in Asia, Europe, Africa, and Brazil 9,15,31,32,50,52 . These differing results are most likely not related to the selected patient groups or to the Leishmania species involved, but rather to the samples that were analyzed.…”