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  • Title: Evaluation of the use of anti-TNF-alpha in an LPS-induced murine model.
    Author: Holmgren C, Esplin MS, Hamblin S, Molenda M, Simonsen S, Silver R.
    Journal: J Reprod Immunol; 2008 Jul; 78(2):134-9. PubMed ID: 18433878.
    Abstract:
    OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha) may play a critical role in inflammatory-mediated preterm labor. Medications blocking the activity of TNF-alpha 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-alpha 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-alpha. After 24h, 10 microg 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-alpha 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-alpha. Pretreatment with anti-TNF-alpha 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-alpha and LPS compared to LPS alone. CONCLUSION: The use of anti-TNF-alpha 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-alpha. Further evaluation of TNF-alpha blockade as a potential treatment for preterm labor is warranted.
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