Serum cytokine profile in the subclinical form of visceral leishmaniasis

Abstract

The factors determining the development or not of visceral leishmaniasis (VL) have not been completely identified, but a Leishmaniaspecific cellular immune response seems to play a fundamental role in the final control of infection. Few studies are available regarding the production of cytokines in the subclinical form of VL, with only the production of IFN-γ and TNF-α known. The aim of the present study was to identify immunological markers for the oligosymptomatic or subclinical form of VL. A prospective cohort study was conducted on 784 children aged 0 to 5 years from an endemic area in the State of Maranhão, Brazil, between January 1998 and December 2001. During 30 consecutive months of follow-up, 33 children developed the oligosymptomatic form of the disease and 12 the acute form. During the clinical manifestations, serum cytokine levels were determined in 27 oligosymptomatic children and in nine patients with the acute form using a quantitative sandwich enzyme immunoassay. In the subclinical form of VL, variable levels of IL-2 were detected in 52.3% of the children, IL-12 in 85.2%, IFN-γ in 48.1%, IL-10 in 88.9%, and TNF-α in 100.0%, with the last two cytokines showing significantly lower levels than in the acute form. IL-4 was not detected in oligosymptomatic individuals. Multiple discriminant analysis used to determine the profile or combination of cytokines predominating in the subclinical form revealed both a Leishmania resistance (Th1) and susceptibility (Th2) profile. The detection of both Th1 and Th2 cytokine profiles explains the self-limited evolution accompanied by the discrete alterations observed for the subclinical form of VL.

Systematic Review of Biomarkers To Monitor Therapeutic Response in Leishmaniasis

“…In contrast, other studies found minimal levels of this cytokine in Indian VL patients (74,90,91). Moreover, TNF-␣ was also present in asymptomatic VL patients (83), complicating the interpretation of TNF-␣ in cases of VL. For CL patients, studies of TNF-␣ serum levels are contradictory; some studies found elevated levels of TNF-␣ in the plasma of CL patients that decreased posttreatment compared to healthy controls (92)(93)(94)(95), but others could confirm this only for MCL patients (85,96).…”

“…TNF-␣ levels were found to be significantly increased in patients with active VL (77,(83)(84)(85); they declined during treatment (85-89) and returned to healthy-control levels at the end of treatment (84). Unresponsive patients retained elevated levels of TNF-␣ (85).…”

“…Moreover, IFN-␥ plasma concentrations appeared to be significantly higher after the end of treatment in patients unresponsive to therapy than in responsive patients treated with sodium stibogluconate (SSG) (74,75). Discrepant results in asymptomatic VL patients indicated that IFN-␥ was elevated in 48% of asymptomatic Brazilian patients but that it was undetectable in the vast majority of asymptomatic Ethiopian patients (67,83). Additionally, a recent study of Brazilian pediatric VL patients showed that low levels of IFN-␥ were associated with signs of severity, such as jaundice or hemorrhage (97).…”

Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features

“…However, despite a highly activated immune system, patients exhibit Leishmania antigenspecifi c immunosuppression 12 . Additionally, interleukin 10 (IL-10) and TGF-β activity in splenic and liver macrophages induces parasite proliferation; therefore, these cytokines can be characterized as immune response regulators [13][14][15][16][17][18] . It has been suggested that the main risk factors for death in VL are related to the fact that such high systemic pro-infl ammatory cytokine production greatly compromises organs and systems 10 .…”

Immunologic Indicators of Clinical Progression during CanineLeishmania infantumInfection

“…Treated individuals develop a cell-mediated immune response capable of offering protection from reinfection, as characterized by antigen-specific IFN-␥ responses (7,34). In contrast, individuals with advanced VL show a decrease in antigen-specific IFN-␥ production and elevated levels of the immunoregulatory cytokine IL-10 in serum and increased IL-10 mRNA expression in lesional tissue (6,10). The correlation between VL disease progression and IL-10 production in humans is now well established (22).…”