Tumor Necrosis Factor (Cachectin) in Human Visceral Leishmaniasis

High tumor necrosis factor-α (TNFα) levels were present in the serum of24 of28 active visceral leishmaniasis (VL) patients (142.9 ± 113.9pg/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 TNFα levels were also not elevated in 15 normal volunteers (11.3 ± 15.6 pg/ml) and in 10 patients with tegumentary leishmaniasis (19.1 ± 10.8pg/ml). Leishmanial infection of human monocyte-derived macrophages enhanced the basal TNFα production by these cells, and this effect was further potentiated by treatment with recombinant interferon-γ, After effectivetreatment ofVL patients, serumTNFα levelsdropped 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 TNFα levels in VL patients are a good parameter to monitor in determining host response to therapy.