Abstract

The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, particularly, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil). We conducted a prospective, descriptive study between May 2008 and December 2009. This study was based on an assessment of all pediatric patients with VL who were observed in a reference hospital in Maranhão. Among 27 children, 55.5% presented with more than one sign of severity or warning sign. Patients without signs of severity or warning signs and patients with only one warning sign had the highest interferon-gamma (IFN-γ) levels, although their interleukin 10 (IL-10) levels were also elevated. In contrast, patients with the features of severe disease had the lowest IFN-γ levels. Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2) and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Our results showed that disease severity was associated with low IFN-γ levels and elevated IL-10 levels. However, further studies with larger samples are needed to better characterize the relationship between disease severity and cytokine levels, with the aim of identifying immunological markers of active-disease severity.

Highlights

  • The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject

  • This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil)

  • Visceral leishmaniasis (VL), which is endemic throughout Brazil, can be lethal if not treated quickly because it is systemic in nature

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Summary

Introduction

The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil). Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2) and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Interleukin 10 (IL-10) and TGF-β activity in splenic and liver macrophages induces parasite proliferation; 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-inflammatory cytokine production greatly compromises organs and systems[10]

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