Tumor Necrosis Factor (Cachectin) in Human Visceral Leishmaniasis

Abstract

High tumor necrosis factor-alpha (TNF alpha) levels were present in the serum of 24 of 28 active visceral leishmaniasis (VL) patients (142.9 +/- 113.9 pg/ml, mean +/- SD), whereas levels were not elevated in 26 of 30 patients with cryptic leishmanial infection (16 asymptomatic, 4 with self-healing subclinical infection, and 10 posttreatment VL cases). Serum TNF alpha levels were also not elevated in 15 normal volunteers (11.3 +/- 15.6 pg/ml) and in 10 patients with tegumentary leishmaniasis (19.1 +/- 10.8 pg/ml). Leishmanial infection of human monocyte-derived macrophages enhanced the basal TNF alpha production by these cells, and this effect was further potentiated by treatment with recombinant interferon-gamma. After effective treatment of VL patients, serum TNF alpha levels dropped rapidly (129 +/- 112 vs. 9 +/- 13 pg/ml in 10 days), even before clinical parameters such as spleen size or parasitism, white blood cell count, or levels of hemoglobin returned to normal values. On the other hand, patients unresponsive to treatment remained with elevated levels (276 +/- 69 vs. 155 +/- 71 pg/ml in 10 days). Thus, serum TNF alpha levels in VL patients are a good parameter to monitor in determining host response to therapy.

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

“…In experimental models using L. donovani (Tumang et al 1994), TNF-α is generally increased during the active disease. In addition, this cytokine has been reported to be a reliable marker of VL that has been cured (Barral-Netto et al 1991), which explains the detection of basal levels of TNF-α in the cured group.…”

The role of complement in the early phase of Leishmania (Leishmania) amazonensis infection in BALB/c mice

“…These data indicate that in normal human serum, natural IgM anti-Leishmania antibodies are the main triggering factor for classical pathway activation by promastigotes, and that serum MBL and C-reactive protein do not contribute significantly to this process (16). On the other hand, MBL levels correlated directly with the probability of developing visceral leishmaniasis and affected the functions of L. chagasi-infected monocytes since the monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted high levels of TNF-α and IL-6 (17), cytokines which can inhibit the leishmanicidal capacity of macrophages infected with L. mexicana (18,19).…”

Genetic analysis of multicase families of visceral leishmaniasis in northeastern Brazil: no major role for class II or class III regions of HLA

“…6,8,9 Also in view of the major role which class I and II genes of the MHC have in presenting antigen to protective or disease exacerbatory CD4 30,31 or CD8 32 T cells, and the high levels of circulating TNF␣ associated with clinical disease in man. 10 There are, of course, many other genes/ mechanisms that regulate these important immunological pathways. The negative result obtained here simply fuels the search for the non-MHC genes and mechanisms…”

“…In man, high levels of circulating tumour necrosis factor ␣ (TNF␣) associated with clinical visceral leishmaniasis 10 suggest that regulatory polymorphisms for genes encoded in other regions of the HLA complex might also be important in determining genetic susceptibility. This would be consistent with a range of other infectious diseases, [11][12][13][14][15][16][17] including mucocutaneous leishmaniasis, 18 where allelic associations between disease and polymorphisms in the gene (TNFA) encoding TNF␣ or the closely linked gene (TNFB) encoding lymphotoxin A (LTA or TNF␤) have been observed.…”