Role of tumor necrosis factor in Listeria resistance of nude mice

Abstract

The effects of sheep anti-murine recombinant tumor necrosis factor-alpha (TNF-α) on resistance to Listeria monocytogenes infection were studied in T cell-deficient nu/nu mice. The sheep anti-TNF-α antibody preparation was specific for TNF since it neutralized 300 U of recombinant murine TNF-α in vitro at a dilution of up to 1/1,000 but did not neutralize 32 U of interferon (IFN)-α, -β or 32 U of IFN-γ in vitro at a 1/20 dilution. When tested in vivo in sublethally Listeria-infected nu/nu or T cell-competent C57BL/6 or ICR mice, a single treatment of 0.2 ml anti-TNF-α given intraperitoneally on either day -1,0 or +1 resulted in the death of mice by day 5–7 due to the uncontrolled growth of Listeria; bacterial counts in spleen and liver were increased on days 3–5 by a factor of 10–1,000 in these organs. When examined histologically, organs from mice with the anti-TNF-α treatment contained more, and considerably bigger, lesions that exhibited central necrosis. The enhancing effect of anti-TNF-α on Listeria infection seemed greater early during Listeria infection on days 1–6 when compared to later phases of the infection around days 6–10. From the data presented we conclude that in addition to other lymphokines, such as IFN-γ, TNF-α is of importance during the entire course of a Listeria infection in nu/nu mice.