Role and effect of TNF-alpha in experimental visceral leishmaniasis.
TNF-alpha has been implicated in cytokine-induced macrophage activation and tissue granuloma formation, two activities linked to control of intracellular visceral infection caused by Leishmania donovani. To determine the role of TNF-alpha in L. donovani-infected BALB/c mice, we measured TNF-alpha levels and treated mice with either anti-TNF-alpha antiserum or TNF-alpha. TNF-alpha activity in infected livers was increased by 2.7-fold 2 wk after challenge and by 5.5-fold at wk 8. In parallel, although control mice acquired resistance by wk 4 and resolved infection by wk 8, liver parasite burdens steadily increased in anti-TNF-alpha-treated animals. Hepatic granuloma formation, however, was not impaired by anti-TNF-alpha. Endogenous TNF-alpha levels provoked by L. donovani appeared sufficient and optimal because exogenous TNF-alpha administration had no beneficial effect on established infection and continuous high-dose treatment impaired antileishmanial activity. Thus, although not required for granuloma formation, endogenous TNF-alpha appears to be critical to both initial acquisition of resistance to L. donovani and resolution of experimental visceral infection.
Tumang
M C
MC
Division of Infectious Diseases, Cornell University Medical College, New York, NY 10021.
Keogh
C
C
Moldawer
L L
LL
Helfgott
D C
DC
Teitelbaum
R
R
Hariprashad
J
J
Murray
H W
HW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000517:prevention & control; D007898:Leishmaniasis, Visceral / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017472:Receptors, Interleukin-1 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha