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

Objectives To study the influence of soluble tumour necrosis factor (TNF) receptors (sTNFR) on bioactivity and immunoreactivity of TNF-α in patients with visceral leishmaniasis (Kala-azar) and to examine the association between circulating levels of sTNFR type I and type II with clinical manifestations of the disease.
Methods   Ten patients with Kala-azar were enrolled. Plasma samples for TNF-α and sTNFR were obtained on days 0, 7 and 21–28 of antimonial therapy. Bioactivity of TNF-α was measured by cytotoxicity to L-929 cells and immunoreactivity by enzyme-linked immunosorbent assay (ELISA). sTNFR-I and sTNFR-II were measured by ELISA.
Results   Measured by ELISA, TNF-α was detected at baseline in all patients (range from 22.3 to 163 pg/mL) and showed a linear decline over time on therapy ( r  = −0.49, P  = 0.007). In contrast, when measured by cytotoxicity assay, TNF-α was detected in only one patient at baseline (193 pg/mL) and in four patients at the end of therapy (38.7, 95, 133 and 232 pg/mL) and there was no linear association between TNF-α and duration of therapy ( r  = −0.18, P  = 0.45). sTNFR-I and sTNFR-II were detected in all patients before therapy. There was a strong positive correlation between plasma concentrations of sTNFR-I and sTNFR-II ( r  = 0.8, P  = 0.006). Levels of sTNFR-I and sTNFR-II declined exponentially with time on therapy.
Conclusions   We concluded that sTNFR-I and sTNFR-II are related to disease activity in patients with Kala-azar and that these circulating receptors may interfere with the biological activity of TNF-α in patients with Kala-azar.