Influence of irbesartan on the urinary excretion of cytokines in patients with chronic kidney disease

Background The non-hemodynamic effects of angiotensin receptor blocker （ARB） in the delay of progression of chronic kidney disease （CKD） remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD. Methods In this randomized perspective clinical trial, different doses of irbesartan （150 mg/d and 300 mg/d） were given to two groups of patients in a cross-over design. Blood pressure （BP）, creatinine clearance （Ccr） and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant. Results Urinary excretion of cytokines （granulocyte colony stimulating factor （GCSF）, intercellular cell adhesion molecule-1 （ICAM-1）, interferon y （IFN-y）, interleukin 1β （IL-1β）, IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1δ （MIP-Iδ） in group B （irbesartan 300 mg/d） was significantly decreased in comparison to group A （irbesartan 150 mg/d） after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels （GCSF, GM-CSF, IFN-γ, IL-1α, IL-11, IL-12p40, MCP-2, MIP-1α）, while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1α by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.Conclusion Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cvtokines excretion in the urine of CKD patients.

Apoptosis of non-tumor cells contributes to increased serum cytochrome c level in a neuroblastoma xenograft model

Background Neuroblastoma （NB） is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c （Cyt c） in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells （KP-N-NS） into nude mice and collected the sera of tumor-bearing mice （n=14） and control mice （n=25） 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight （SELDI-TOF） mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio （m/z） of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography （HPLC）.Liquid chromatography coupled with tandem mass spectrometry （LC-MS/MS） was performed to produce peptide mass fingerprints （PMFs）.Spectrum analysis and a database search revealed that the highly expressed protein （m/z=11605.4） from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.