Serum cytokines associated with severity and complications of kala-azar

Abstract

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.

Predicting death from kala-azar: construction, development, and validation of a score set and accompanying software

“…It was also included in the scoring model developed by Coura-Vital et al (6) but not those developed by Sampaio (28) and Werneck (24) , due to age restrictions and earlier data collection, respectively, before HIV-1 co-infection became a major problem for patients with kala-azar. The higher mortality for kala-azar in HIV-1-infected patients is likely affected by the lower cluster of differentiation 4 (CD4) count with kala-azar itself, increasing the vulnerability to other co-infections (41) , and to the more intense systemic infl ammation when compared with patients without HIV-1 infection, as demonstrated previously (35) . Therefore, addressing other co-infections and systemic infl ammation are important steps in the treatment of these patients.…”

“…Since thrombocytopenia is, similar to other markers of DIC such as fi brin degradation products and d-dimer, strongly correlated with γ-interferon and IL-6 (35) , the conclusion would be that thrombocytopenia in kala-azar is mostly a result of consumption by DIC. However, the usual large splenomegaly, typical of kala-azar, is an obvious competing explanation for thrombocytopenia.…”

“…Other prognostic studies (not of scoring models) also revealed the importance of younger age and that old age is a strong risk factor for kala-azar-related death (2) (5) (19) (28) (34). One possible explanation is the higher concentrations of infl ammatory and anti-infl ammatory cytokines in these age groups (35) (36) (37) (38) (39) (40) .…”

“…Apparently, both factors act synergistically to hamper hemostasis and sustain bleeding. Furthermore, DIC in kala-azar is clearly linked to systemic infl ammation, particularly to serum γ-interferon and interleukin (IL)-6 (35) .…”

“…Similar to hemorrhage, they were more relevant for children than for older children and adults and a consequence of systemic infl ammation (35) . When present, patients may need supplementary symptomatic therapy such as intravenous albumin due to the typical low serum albumin concentration, as well as respiratory support and antiemetics; however, the basic cause of infl ammation will remain unaffected.…”