Role of tumor necrosis factor in Listeria resistance of nude mice.
The effects of sheep anti-murine recombinant tumor necrosis factor-alpha (TNF-alpha) on resistance to Listeria monocytogenes infection were studied in T cell-deficient nu/nu mice. The sheep anti-TNF-alpha antibody preparation was specific for TNF since it neutralized 300 U of recombinant murine TNF-alpha in vitro at a dilution of up to 1/1,000 but did not neutralize 32 U of interferon (IFN)-alpha, -beta or 32 U of IFN-gamma 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-alpha 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-alpha treatment contained more, and considerably bigger, lesions that exhibited central necrosis. The enhancing effect of anti-TNF-alpha 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-gamma, TNF-alpha is of importance during the entire course of a Listeria infection in nu/nu mice.
Hauser
T
T
Laboratory of Experimental Pathology, University Hospital Zurich, Switzerland.
Frei
K
K
Zinkernagel
R M
RM
Leist
T P
TP
D000818:Animals; D002470:Cell Survival; D004352:Drug Resistance, Microbial; D008089:Listeria monocytogenes / Q000187:drug effects*; D008088:Listeriosis / Q000188:drug therapy*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha