Kupffer cells (KC), resident macrophages of the liver, have been strongly implicated in lipopolysaccharide (LPS)-induced liver graft injury. However, our recent study showed that sizofiran (schizophyllan glucan) (SPG), which activates KC, did not influence cold ischemia-reperfusion liver injury of LPS-exposed rats. Here we investigated some mechanisms by which SPG does not aggravate LPS-enhanced cold ischemia-reperfusion rat liver injury. Control and SPG-treated rats were exposed to LPS for 2 h prior to hepatectomy. The livers were cold-preserved in University of Wisconsin solution followed by reperfusion with Krebs-Henseleit buffer. We found that SPG dramatically inhibited LPS-induced increases of tumor necrosis factor-α (TNF-α) in the plasma and bile in vivo. Moreover, LPS-induced TNF- release into the washout solution after cold ischemia was also abrogated by SPG pretreatment. However, SPG increased TNF-α release into the perfusate after reperfusion. On the other hand, SPG completely abolished expression of c-myc protooncogene, which is known to sensitize cells to TNF-α cytotoxicity. In conclusion, inhibition of both TNF-α release after LPS challenge and c-myc expression may explain why activation of KC with SPG does not aggravate endotoxin-enhanced cold ischemia-reperfusion liver injury.
Cytokines play a critical and multifarious role in follicular maturation. Consequently, they may influence the pregnancy outcome in cycles of assisted reproduction. The aim of this study was to measure the levels of tumor necrosis factor-α(TNFα), vascular endothelial growth factor (VEGF) and leptin in serum and follicular fluids (FFs) from women undergoing controlled ovarian hyperstimulation (COH) for intracytoplasmic sperm injection cycles (ICSI). We tried to investigate their interrelationships and to evaluate them as predictive markers for the cycle’s outcome. Seventeen
women participated in this study. Male factor infertility was the only indication for ICSI cycles. For COH, the long agonist protocol with triptorelin and recombinant FSH was employed. Cytokines levels were evaluated by ELISA. Serum cytokine levels did not differ between pregnant and non-pregnant women. FF-VEGF levels were significantly
elevated in non-pregnant women (722.2±1093.2 pg/ml) as compared to pregnant women (290.3±259.8 pg/ml). Leptin concentrations were also significantly higher in FFs of non-pregnant women (682.6±625.1 ng/ml) than those of pregnant women (231.6±286.5 ng/ml). There were significant
positive correlations between FF-leptin and age, as well as between FF-leptin and FF-VEGF concentrations. It was concluded that elevated FF-leptin and VEGF levels are associated with failure of conception in IVF cycles and may serve as markers in clinical practice.