Wasting and macrophage production of tumor necrosis factor/cachectin and interleukin 1 in experimental visceral leishmaniasis.
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/10(6) 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/10(6) mononuclear cells/24 hr (P = 0.005). Control hamsters produced 7.7 +/- 2.7 pg IL-1/10(6) 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-1/10(6) mononuclear cells/24 hr (P = 0.002). In comparison to infected animals, mononuclear cells from control hamsters incubated with lipopolysaccharide, 10 micrograms/ml, produced 172.5 ng TNF and 44.6 pg of IL-1/10(6) 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.
Pearson
R D
RD
University of Virginia School of Medicine, Charlottesville.
Cox
G
G
Evans
T
T
Smith
D L
DL
Weidel
D
D
Castracane
J
J
D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000503:physiopathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D004435:Eating; D007375:Interleukin-1 / Q000378:metabolism*; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000503:physiopathology*; D008647:Mesocricetus; D010586:Phagocytes / Q000469:parasitology; D013154:Spleen / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha