Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/7260
Title: Serum cytokines associated with severity and complications of kala-azar
Authors: Costa, Dorcas Lamounier
Rocha, Regina L
Carvalho, Rayssa Maria de Araujo
Lima Neto, Adelino S
Harhay, Michael O
Costa, Carlos Henrique Nery
Barral Netto, Manoel
Barral, Aldina Maria Prado
Affilliation: Federal University of Piauí. Maternal and Childhood Department. Piauí, Brasil / Institute of Tropical Medicine ‘Natan Portella’. Laboratory of Leishmaniasis. Piauí, Brasil
Federal University of Minas Gerais. Department of Pediatrics. Minas Gerais, BH, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratorio de Imunoparasitologia. Salvador, BA, Brasil
Institute of Tropical Medicine ‘Natan Portella’. Laboratory of Leishmaniasis. Piauí, Brasil. / Federal University of Minas Gerais. Department of Community Medicine. Minas Gerais, BH, Brasil
Federal University of Minas Gerais. Department of Community Medicine. Minas Gerais, BH, Brasil
Institute of Tropical Medicine ‘Natan Portella’. Laboratory of Leishmaniasis. Piauí, Brasil. / Federal University of Minas Gerais. Department of Community Medicine. Minas Gerais, BH, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunoregulação. Salvador, Bahia, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunoparasitologia. Salvador, BA, Brasil
Abstract: Objectives: Recent clinical data suggest that severe kala-azar (or visceral leishmaniasis) is an exaggerated innate immune response mediated by inflammatory cytokines, leading to a systemic inflammatory syndrome similar to what is observed in malaria, sepsis and other diseases. We tested this hypothesis by measuring serum cytokines in individuals with kala-azar. Methods: We compared patients with severe kala-azar (i.e. hemorrhagic manifestations, n538) with patients without evidence of hemorrhage (n596). We conducted a detailed clinical and laboratory evaluation, measuring serum IL-1beta, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and TNF-alpha, and markers of disseminated intravascular coagulation (DIC). Results: Infants had higher levels of inflammatory cytokines, while HIV-infected patients had lower concentrations of IL-10 and interferon-gamma. Higher levels of IL-6, interferon-gamma, and IL-8 were found among deceased patients. IL-8 and interferon-gamma were independently associated with bleeding. Several cytokines were associated with different signs of severe clinical and laboratory manifestations, including DIC. IL-6 was highly positively and independently associated with IL-1beta, IL-8, IL-10, and negatively associated with TNF-alpha. IL-1beta and TNF-alpha were also highly independently associated with disease severity. Conclusion: In its severe form, kala-azar, a neglected tropical disease, initiates a systemic inflammatory response that leads to DIC and other manifestations. Children may have higher risk of death due to the more intense cytokine release. The data supports the notion that IL-6 is the central cytokine that is associated with lethal disease, but interferon-gamma, IL1beta, IL-8, and TNF-alpha are also involved with disease severity. Inhibition of IL-6 is a potential target of adjuvant therapy for severe or pediatric forms of this disease.
Keywords: Cytokines
Kala-azar
Leishmania infantum
Disseminated intravascular coagulation
Systemic inflammatory response
Issue Date: 2013
Publisher: W. S. Maney & Son Ltd
Citation: COSTA, D. et al. Serum cytokines associated with severity and complications of kala-azar. Pathogens and Global Health, v.107, p.78-87, 2013.
DOI: 10.1179/2047773213Y.0000000078
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

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