Evaluation of the use of anti-TNF-α in an LPS-induced murine model

Holmgren, C.; Esplin, M.S.; Hamblin, S.; Molenda, M.; Simonsen, S.; Silver, R.

doi:10.1016/j.jri.2007.11.003

« Previous Next »Journal of Reproductive Immunology
Volume 78, Issue 2 , Pages 134-139, July 2008

Evaluation of the use of anti-TNF-α in an LPS-induced murine model

C. Holmgren
- University of Utah Health Sciences Center, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA
- Intermountain Health Care, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA
- Corresponding author at: Room 2B, 200 SOM, 30 North 1900 East, Salt Lake City, Utah 84132, USA.
M.S. Esplin
- University of Utah Health Sciences Center, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA
- Intermountain Health Care, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA
S. Hamblin
- University of Utah Health Sciences Center, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA
M. Molenda
- Centacor, Malvern, PA, USA
S. Simonsen
- University of Utah Health Sciences Center, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA
R. Silver
- University of Utah Health Sciences Center, Department of Obstetrics and Gynecology, Salt Lake City, UT, USA

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.

Keywords: Anti-TNF-α, Fetal death, Preterm delivery