TNF-alpha has been implicated in cytokine-induced macrophage activatio
n and tissue granuloma formation, two activities linked to control of
intracellular visceral infection caused by Leishmania donovani. To det
ermine the role of TNF-alpha in L. donovani-infected BALB/c mice, we m
easured TNF-alpha levels and treated m ice with either anti-TNF-alpha
antiserum or TNF-alpha. TNF-alpha activity in infected livers was incr
eased by 2.7-fold 2 wk after challenge and by 5.5-fold at wk 8. In par
allel, although control mice acquired resistance by wk 4 and resolved
infection by wk 8, liver parasite burdens steadily increased in anti-T
NF-alpha-treated animals. Hepatic granuloma formation, however, was no
t impaired by anti-TNF-alpha. Endogenous TNF-alpha levels provoked by
L. donovani appeared sufficient and optimal because exogenous TNF-alph
a administration had no beneficial effect on established infection and
continuous high-dose treatment impaired antileishmanial activity. Thu
s, 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.