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.
Division of Infectious Diseases, Cornell University Medical College, New York, NY 10021.
M C
MC
Tumang
C
C
Keogh
L L
LL
Moldawer
D C
DC
Helfgott
R
R
Teitelbaum
J
J
Hariprashad
H W
HW
Murray
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