Increased levels of IL-10, IL-12, and IFN- in patients with visceral leishmaniasis

Abstract

Visceral leishmaniasis remains a serious public health problem in developing countries. Cytokines have a crucial role in the pathogenesis of this disease. We evaluated plasma levels of IL-10, IL-12 and IFN-γ γ γ γ γ in 32 patients with active visceral lieshmaniasis, in 29 siblings of the patients and in 23 normal individuals in an endemic area to look for correlations between the clinical outcome of infection and the plasma cytokine levels. An analysis was made with a skin test and a quantitative sandwich enzyme immunoassay. Data were analyzed with the Mann Whitney test and the Kruskal Wallis test. The cytokine levels were significantly higher in the patients than in the control groups. We concluded that normalization of the plasma level of IFN-γ γ γ γ γ can serve as a reliable parameter for considering the patient as cured. Key-Words: Visceral leishmaniasis, interleukin, interferon.Visceral leishmaniasis (VL), also known as Kalaazar, is an important health problem in developing countries and is endemic in theMiddle East and Mediterranean regions [1,2]. Northwestern and southern Iran are focal regions for VL, which mainly affects children; consequently, Leishmania infantum is expected to be the dominant type of leishmania in Iran [3,4]. This disease can be asymptomatic, subclinical and self limiting or can develop into clinically manifesting disease [5,6].The factors that determine the development or not of VL have not yet been completely identified, but a leishmania specific cellular immune response seems to play a fundamental role in the control of infection [7,8]. We know that resistance to disease in VL is determined by an appropriate type 1 response, whereas susceptibility is mediated by a type 2 response, characterized by the stimulation of high titers of antibody production [9]. In VL, susceptibility is associated with an inability to produce a macrophage -stimulating cytokine profile (Th1 profile), including interferon gamma (IFN-γ) and interleukin -12 (IL-12); instead, production of immunosuppressive cytokines, such as interleukin 10 (IL-10), (Th2 profile) is observed (10).Few studies have examined the production of cytokines in the families of patients and normal individuals in endemic areas. We evaluated the plasma levels of INF-γ, IL-10, and IL-12 in patients with VL and in their asymptomatic siblings in order to determine if there was a correlation between the clinical symptoms of the disease and cytokine production. Material and MethodsAll patients admitted with a diagnosis of VL in the infectious disease ward of Nemazi hospital, Shiraz, Iran, were categorized as Group I. Group I consisted of 32 cases newly identified as VL patients, based on clinical manifestation of kalaazar, such as anemia, hepatosplenomegally, fever, with a positive bone marrow smear, or IFA (immunoflurescent antibody) ≥1/128. Group II consisted of 29 asymptomatic siblings of these patients living in the endemic area. Group III consisted of 27 asymptomatic individuals from the same endemic area with a positive leishmania skin t...

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.…”

“…A comparison of cured and asymptomatic subjects showed no significant difference in the serum levels of the cytokines assayed, which is in agreement with studies conducted in Iran (Khoshdel et al 2009) and Brazil (Peruhype-Magalhães et al 2005). These findings indicate that, after the infection is cured, the immune response is effective in controlling the disease, followed by the establishment of protective mechanisms similar to those that occur in asymptomatic individuals (Peruhype-Magalhães et al 2005).…”

“…IL-12 also plays a key role in the initiation and maintenance of Th1 responses and the subsequent production of IFN-γ (Ghalib et al 1995). However, studies using the sera of patients with VL from Iran (Khoshdel et al 2009), southeast Ethiopia (Hailu et al 2005) and Brazil (Caldas et al 2005) have shown significantly higher levels of IL-12 in patients with the active disease relative to those in asymptomatic and healthy subjects.…”

“…The plasma concentrations of both IFN-γ and IL-10 are higher in patients with the active disease relative to asymptomatic individuals and are also higher in asymptomatic individuals compared to uninfected individuals (Ansari et al 2006, Khoshdel et al 2009). However, the basal levels of these cytokines have been detected in asymptomatic cases from Brazil, a finding that requires Key words: cytokines -visceral leishmaniasis -clinical forms further investigation (Peruhype-Magalhães et al 2006).…”

“…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). …”