Plasma levels of tumor necrosis factor-alpha in patients with visceral leishmaniasis (Kala-Azar). Association with activity of the disease and clinical remisson following antimonial therapy

Abstract

Evaluation of TNF-alpha in patients with Kala-azar has drawn increasing interest due to its regulatory role on the immune system, in addition to its cachetizing activity. The objective of this study was to examine the association between plasma levels of TNF-alpha, measured by immunoreactivity (ELISA) and bioactivity (cytotoxicity assay with L-929 cells), and clinical manifestations of visceral leishmaniasis. Plasma samples from 19 patients with Kala-azar were obtained before, during and at the end of antimonial therapy. TNF-alpha determinations was done by using the cytotoxicity assay (all patients) and the enzyme-linked immunoassay (ELISA-14 patients). A discrepancy between results obtained by ELISA and cytotoxicity assay was observed. Levels of circulating TNF-alpha, assessed by ELISA, were higher in patients than in healthy controls, and declined significantly with improvement in clinical and laboratory parameters. Plasma levels before treatment were 124.7 +/- 93.3 pg/ml (mean +/- SD) and were higher than at the end of therapy 13.9 +/- 25.1 pg/ml (mean +/- SD) (p = 0.001). In contrast, plasma levels of TNF-alpha evaluated by cytotoxicity assay did not follow a predicted course during follow-up. Lysis, in this case, might be not totally attributed to TNF-alpha. The discrepancy might be attributed to the presence of factor(s) known to influence the release and activity of TNF-alpha.

Anti-parasite therapy drives changes in human visceral leishmaniasis-associated inflammatory balance

“…Our results validated previously published data showing altered levels of cytokines such as TNF-α, TGF-β1, IL-6, IL-8, IL-10 and IL-12p70 in patients with active VL, which reverted to values observed in healthy controls after anti-parasite treatment 17, 21, 27, 29, 33–35 . In addition, high levels of TNF-α, IL-1β, IL-6 and IL-8 have been independently implicated with disease severity and death associated with VL 2, 18 .…”

“…In the present study, we simultaneously assessed serum levels of two major prostanoids already described by our group in tegumentary leishmaniasis, PGE 2 11, 15 and PGF 2 α 13 , as well as other lipid mediators such as LTB 4 and RvD1 11 . In addition, we assessed levels of key cytokines associated with inflammation and also previously linked to VL pathogenesis IL-1β 2 , IL-6 2, 4, 16–18 , IL-8 2, 4, 19 , IL-10 4–6, 16, 20–26 , IL-12p70 4, 22 , TNF-α 4, 18, 21, 27–29 , and TGF-β1 19, 24, 30, 31 (Table 2). We found that VL patients exhibited a very distinct expression profile compared with uninfected healthy controls (Table 2).…”

Serum cytokine profile in the subclinical form of visceral leishmaniasis

“…The deficient production of IFN-γ after exposure to Leishmania antigen is one of the commonly reported factors and is associated with an increase in CD4+ Th cells expressing a Th2 cytokine profile (susceptibility), with the production of IL-4, IL-10 and TNF-α but not of IL-2 or IL-12 (8,(15)(16)(17)(18). The variation in the detectable levels of IL-10 and TNF-α observed in the present study for the acute form has also been described by others (19)(20)(21). Thus, the Th2 profile with oscillating cytokine levels detected in the present study for cases characterized as the acute form of the disease is in agreement with data reported in the literature (22,23).…”

Circulating levels of sTNFR and discrepancy between cytotoxicity and immunoreactivity of TNF-α in patients with visceral leishmaniasis

“…Patients with visceral leishmaniasis often present with weakness, weight loss, and anaemia; symptoms that could be mediated by TNF‐α[5]. Circulating TNF‐α has been detected in patients with visceral leishmaniasis[6–7] and its presence has been related to disease activity[8,9].…”