Evaluation of the use of anti-TNF-α in an LPS-induced murine model
Received 31 May 2007; received in revised form 1 October 2007; accepted 6 November 2007. published online 23 April 2008.
Abstract
Objective
Tumor necrosis factor α (TNF-α) may play a critical role in inflammatory-mediated preterm labor. Medications blocking the activity of TNF-α have been shown to be effective in the treatment of conditions such as rheumatoid arthritis; however, the use of these medications for an event like preterm birth or fetal death is unknown. We hypothesized that treatment with anti-TNF-α may decrease the rate of fetal death and preterm birth in a LPS-induced murine model.
Methods
Pregnant C57BL/6J mice received intraperitoneal (IP) injections of either vehicle or 2mg anti-TNF-α. After 24h, 10μg of LPS was administered IP. Mice were sacrificed 24h later and outcomes between groups were assessed. A second set of experiments utilizing RT-PCR was performed to determine the influence of anti-TNF-α on production of inflammatory cytokines in response to LPS.
Results
There were 72 resultant pups in the LPS+saline group, and 91 in the group receiving LPS+anti-TNF-α. Pretreatment with anti-TNF-α reduced the rate of fetal death and preterm birth after LPS administration (p<0.01). Expression of IL-6, IL-1beta, TLR-2, CD14 and COX-1 were found to be significantly reduced in mice treated with anti-TNF-α and LPS compared to LPS alone.
Conclusion
The use of anti-TNF-α decreased fetal deaths and preterm deliveries in an LPS-induced model of preterm birth. In addition, there were critical gene expression alterations in the group receiving anti-TNF-α. Further evaluation of TNF-α blockade as a potential treatment for preterm labor is warranted.
ABSTRACT