Cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alp
ha) inhibit the intracellular replication of Chlamydia pneumoniae or Chlamy
dia trachomatis. In this study, we found that another cytokine, lymphotoxin
(TNF-beta), restricts the growth of C. pneumoniae in HEp-2 cells. When lym
photoxin (10 U/ml) was added during incubation from 8 to 16 h postinoculati
on, inclusion body formation was severely reduced. In addition, we observed
activation of nitric oxide production and the nuclear transition of NF-kap
pa B in HEp-2 cells in response to lymphotoxin. These results suggest that
inhibition of chlamydial growth by lymphotoxin is mediated, at least in par
t, by nuclear transition of NF-kappa B, resulting in induction of nitric ox
ide synthase to produce nitric oxide, a potent bacteristatic agent. This is
the first report on antichlamydial activity of lymphotoxin through inducti
on of nitric oxide.