Wasting and Macrophage Production of Tumor Necrosis Factor/Cachectin and Interleukin 1 in Experimental Visceral leishmaniasis

Richard D. PearsonUniversity of Virginia School of Medicine, ENDOGEN Inc., Charlottesville, Virginia

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Gary CoxUniversity of Virginia School of Medicine, ENDOGEN Inc., Charlottesville, Virginia

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Thomas EvansUniversity of Virginia School of Medicine, ENDOGEN Inc., Charlottesville, Virginia

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Deirdre L. SmithUniversity of Virginia School of Medicine, ENDOGEN Inc., Charlottesville, Virginia

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Denise WeidelUniversity of Virginia School of Medicine, ENDOGEN Inc., Charlottesville, Virginia

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John CastracaneUniversity of Virginia School of Medicine, ENDOGEN Inc., Charlottesville, Virginia

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Wasting and secretion of the catabolic cytokines tumor necrosis factor (TNF)/cachectin and interleukin 1 (IL-1) were assessed in weanling Syrian hamsters infected with Leishmania donovani amastigotes. Whereas the mean weight of uninfected animals increased progressively over 9 weeks, the mean weight of infected animals plateaued at 4–6 weeks and then decreased progressively until death. Splenic mononuclear cells from control hamsters produced 11.3 ± 8.3 (SD) ng TNF/106 mononuclear cells/24 hr. TNF secretion in infected animals was greater than the mean ± 2 SD of controls in 1 of 3 hamsters at 2 weeks post-infection and in 8 of 9 hamsters at weeks 4–8. The mean TNF secreted by infected animals studied at weeks 4–8 was 371 (range 28–800) ng TNF/106 mononuclear cells/24 hr (P = 0.005). Control hamsters produced 7.7 ± 2.7 pg IL-1/106 mononuclear cells/24 hr. At 2 weeks, mononuclear cells from 2 of 3 infected animals secreted amounts of IL-1 greater than the mean ± 2 SD of controls. All of 8 infected hamsters secreted increased amounts of IL-1 at 4–8 weeks. The mean was 164 (range 17–370) pg IL-1/106 mononuclear cells/24 hr (P = 0.002). In comparison to infected animals, mononuclear cells from control hamsters incubated with lipopolysaccharide, 10 µg/ml, produced 175.5 ng TNF and 44.6 pg of IL-1/106 mononuclear cells/24 hr. The effect of visceral leishmaniasis on food intake was assessed in a separate group of animals housed individually in metabolic cages. Significant reductions in weight and food intake were first observed at 2 and 3 weeks of infection, respectively. By 5 weeks, the food intake of infected animals was 46% that of controls. Syrian hamsters infected with L. donovani provide an excellent model with which to study the mechanism of wasting.

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