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Comparative Study
. 2013 Mar;107(2):78-87.
doi: 10.1179/2047773213Y.0000000078.

Serum cytokines associated with severity and complications of kala-azar

Dorcas L Costa  1 , Regina L Rocha, Rayssa M A Carvalho, Adelino S Lima-Neto, Michael O Harhay, Carlos Henrique N Costa, Manoel Barral-Neto, Aldina P Barral
Affiliations
Comparative Study

Serum cytokines associated with severity and complications of kala-azar

Dorcas L Costa et al. Pathog Glob Health. 2013 Mar.

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, n = 38) with patients without evidence of hemorrhage (n = 96). 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.

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Figures

Figure 1
Figure 1
Box plots of the serum concentration of cytokines in patients with kala-azar according to the occurrence of death.
Figure 2
Figure 2
Box plots of the serum concentration of cytokines in patients with kala-azar according to the presence of bleeding, edema, and vomiting. Only statistically significant association results are shown.
Figure 3
Figure 3
Correlation of serum cytokines concentration with the results of laboratory tests in patients with kala-azar.
Figure 4
Figure 4
Correlation of serum cytokines concentration with platelet count and D-dimer levels.
Figure 5
Figure 5
Box plots of the concentration of serum cytokines in patients with kala-azar according to the detection of fibrin degradation products.
Figure 6
Figure 6
Mutual correlation of serum cytokines in patients with kala-azar.
See this image and copyright information in PMC

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