Antiinflammatory properties of IL-10 rescue small-for-size liver grafts.

The present study aims to investigate the potential therapeutic role of interleukin-10 (IL-10) in small-for-size liver transplantation. A syngenic rat orthotopic liver transplantation model was performed using either whole or 40% liver volume of Lewis rats as grafts according to the experimental design. IL-10 was given to the 40% grafts right after reperfusion, and also at 24 and 48 hours after transplantation. When no treatment was given, less than 40% of the small-for-size grafts survived indefinitely, whereas IL-10 treatment could increase the long-term survival rate of the small-for-size grafts to 80%. The 40% grafts presented with extensive areas of necrosis and increased number of apoptotic cells at the early phases after reperfusion. In addition, upregulation of plasma protein carbonyl content (PCC) levels was also detected in the 40% graft group. IL-10 treatment suppressed the upregulation of allograft inflammatory factor-1 (AIF-1) on macrophages in the 40% grafts, and at the same time, decreased the levels of plasma PCC, and improved the histology and function of the 40% grafts. The expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-alpha, and caspase 9 in the 40% grafts were upregulated after reperfusion, whereas the augmentation could be suppressed by the administration of IL-10. Finally, IL-10 culture could block AIF-1-mediated NO production and downregulate the expression of iNOS and TNF-alpha in a macrophage cell line. In conclusion, IL-10 rescued the small-for-size liver grafts by its antiinflammatory properties, through inhibition of AIF-1 mediated proinflammatory and proapoptotic activities of the macrophages during the early period after ischemia/reperfusion.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry serum protein profiling to identify nasopharyngeal carcinoma.

BACKGROUND: Diagnosis of nasopharyngeal carcinoma (NPC) at an early disease stage is important for successful treatment and improving the outcome of patients. The use of serum protein profiles and a classification tree algorithm were explored to distinguish NPC from noncancer. METHODS: Serum samples were applied to metal affinity protein chips to generate mass spectra by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Protein peak identification and clustering were performed using the Biomarker Wizard software. Proteomic spectra of serum samples from 50 NPC patients and 54 noncancer controls were used as a training set and a classification tree with 6 distinct protein masses was generated by using Biomarker Pattern software. The validity of the classification tree was then challenged with a blind test set including another 20 NPC patients and 25 noncancer controls. RESULTS: The software identified an average of 93 mass peaks/spectrum and 6 of the identified peaks were used to construct the classification tree. The classification tree correctly determined 83% (123 of 149) of the test samples with 83% (58 of 70) of the NPC samples and 82% (65 of 79) of the noncancer samples. In a combination of the serum protein profiles with Epstein-Barr (EBV) nuclear antigen 1 (EBNA1 IgA) test, the diagnostic sensitivity and specificity were increased to 99% and 96%, respectively. CONCLUSIONS: The results suggest that SELDI-TOF-MS serum protein profiles could discriminate NPC from noncancer. The combination of serum protein profiles with an EBV antibody serology test could further improve the accuracy of NPC screening.

Linking inflammation to acute rejection in small-for-size liver allografts: the potential role of early macrophage activation.

This study aims to investigate the immunological status of small-for-size liver allografts and possible mechanism that contributes to the accelerated immune response in these allografts. Eight experimental groups were: whole isografts; 40% isografts; whole allografts, no treatment; 40% allografts, no treatment; whole allografts with sodium salicylate intraperitoneal injection, D0-3; 40% allografts with sodium salicylate, D0-3; whole allografts with FK506 intramuscular injection D0-3, and 40% allografts with FK506, D0-3. The 40% allografts survived significantly shorter than whole allografts (p=0.02). At 72 h after reperfusion, a higher number of macrophages infiltrated into the periportal area of small-for-size allografts than whole allografts. Remarkable up-regulation of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) messenger RNA (mRNA) levels were detected in small-for-size allografts within 24 h after reperfusion. Sodium salicylate administration reduced IL-1beta and IFN-gamma mRNA in both small-for-size and whole allografts, but it could decrease IL-2 and IL-10 mRNA levels only in small-for-size allografts. In vitro study revealed that CD80, CD86 and CD11b expression on macrophages was augmented after IL-1beta stimulation, whereas the up-regulation could be blocked by sodium salicylate. In conclusion, early activation of macrophages as a result of graft injury might play an important role in the accelerated acute rejection process in small-for-size allografts.