Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia/reperfusion-injured rats via suppression of the TLR2/NF-κB pathway.

INTRODUCTION: The inflammatory response plays an important role in liver dysfunction after hepatic ischemia/reperfusion (I/R), which is tightly regulated by the Toll-like receptor 2 (TLR2)/nuclear factor (NF)-κB pathway; suppression of TLR2/NF-κB signaling has therefore become a promising target for anti-inflammatory treatment in hepatic I/R injury. Erythropoietin (EPO) is a glycoprotein cytokine produced primarily by the kidney that has anti-inflammatory activities. The purpose of the present study was to investigate the effect of EPO preconditioning, if any, against hepatic I/R injury in rats and its underlying mechanisms. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to partial (70%) hepatic ischemia for 45 minutes after pretreatment with either saline or EPO followed by 24-hour reperfusion. Hepatic injury was evaluated according to biochemical and histopathologic examinations. The expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were measured by using enzyme-linked immunosorbent assay and real-time polymerase chain reaction. The expression of nuclear translocation and phosphorylation of NF-κB p65, EPOR receptor (EPOR), p-EPOR, p-IκB-α, IκB-α, and TLR2 were determined by using Western blot analysis. RESULTS: EPO treatment significantly improved hepatic function and histology, as indicated by reduced transaminase levels and pathologic changes. The expression of TNF-α, IL-1ß, IL-6, p-IκB-α, and TLR2 was significantly decreased with up-regulation of p-EPOR by EPO. Moreover, EPO pretreatment also reduced I/R-induced the phosphorylation and nuclear translocation of NF-κB p65 subunits in liver tissue, but EPO had no influence on the expression of p65 and IκB-α. CONCLUSIONS: These results suggest that EPO pretreatment ameliorates hepatic I/R injury, which is involved in suppressing TLR2/NF-κB-mediated inflammation.

Clofazimine-mediated augmentation of LPS-induced tumor necrosis factor production in macrophages.

Tumor necrosis factor (TNF) exerts multiple biological activities including immune response. It is also believed to play an important role in anti-bacterial response. In this study in vitro, we observed augmentation of LPS-induced TNF production from mouse macrophages by clofazimine treatment. Rifampicin, however, did not indicate such an activity. Clofazimine itself, on the other hand, did not have any TNF-inducing activity. Clofazimine is a well known anti-leprosy drug; in addition, from the results obtained here, this drug could induce anti-M. leprae response of host by way of the augmented immune response by enhanced cytokine production from macrophages.

[A ten-year retrospective investigation of serum against EHF antibodies in Nanchong District, Sichuan].

This paper reports a retrospective inquiry of blood serum against epidemic hemorrhagic fever (EHF) antibodies in some of our hospital treated EHF patients during 1974-1984. It was found that the total positive rate of sera against EHF antibodies obtained from different periods of EHF patients was 86.8% (170/196). The titers were highest in patients who had been attacked within one year and the titers markedly decreased from the second year onwards. However certain level of serum titre could be detected up to 8th-10th year after the acute infection. Normal persons in high-incidence districts and medical workers who had kept in close contact for many years with EHF patients were found to be negative. It is presumed that this disease's latent infection is probably very low.