Evaluation of the effect of anti-macrophage migration inhibitory factor antibody in a mouse model of lipopolysaccharide-induced preterm delivery

Objective: Pro-inflammatory cytokines are considered as important for the onset of preterm labour and maternal and/or fetal inflammatory response is suggested to play a role in the pathophysiology of preterm labour. Macrophage migration inhibitory factor (MIF) regulates inflammatory responses, inducing the expression of pro-inflammatory mediators and functioning to counterbalance the anti-inflammatory effects of glucocorticoids. MIF may play a role in infection-associated preterm birth. We investigated the preventive effect of anti-MIF antibody on lipopolysaccharide-induced preterm birth in mice.Method: On day 17 of gestation, Lipopolysaccharide (LPS) was administered intraperitoneally to pregnant Balb/c mice to induce preterm delivery. For the first set of experiments, to investigate the effect of anti-MIF antibody on duration of gestation and fetal weigth, dams were treated intraperitoneally with anti-MIF antibody at the same time as LPS treatment, or 2 h before LPS treatment. A second set of experiments was performed to determine the influence of anti-MIF antibody on intrauterine production of tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6). The mice were sacrificied 8 h after LPS injection and then samples of gestational tissues were obtained.Results: The duration of gestation in treatment with anti-MIF antibody before 2 h LPS injection was significantly longer than LPS treated mice (P=.004). By contrast, treatment with anti-MIF antibody at the same time as LPS injection had no effect on duration of gestation. TNF-? and IL-6 concentration in gestational tissues was significantly reduced in mice treated with anti-MIF antibody at the same time as LPS treatment ( P= .010 ve .025), or 2 h before LPS treatment ( P= .010 ve .006) compared to LPS alone.Conclusion: We have demonstrated for the first time that anti-MIF antibody can delay LPS-induced preterm birth in mice. Results from these study suggest that MIF play a role in the pathophysiology of preterm labour.