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

ObjectiveTumor 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.MethodsPregnant C57BL/6J mice received intraperitoneal (IP) injections of either vehicle or 2 mg anti-TNF-α. After 24 h, 10 μg of LPS was administered IP. Mice were sacrificed 24 h 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.ResultsThere 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.ConclusionThe 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.