24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus.

      The Journal of rheumatology
      Animals, Antigens, CD95, immunology, Biological Markers, metabolism, Female, Humans, Inflammation, Interferon-gamma, Interleukin-10, genetics, Interleukin-6, deficiency, Kidney, cytology, pathology, Life Expectancy, Lupus Erythematosus, Systemic, physiopathology, therapy, Lupus Nephritis, Mice, Mice, Inbred BALB C, Mice, Inbred MRL lpr, Mice, Knockout, Proteinuria, Signal Transduction, physiology, Spleen, Vascular Cell Adhesion Molecule-1

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Fas(lpr) mice. We generated IL-6-deficient MRL-Fas(lpr) mice using a backcross/intercross breeding scheme. Renal pathology was evaluated using immunohistochemistry detection for macrophages, lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), and TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick end-labeling) for apoptotic cells, and renal IgG and C3 deposition by immunofluorescence staining. Expression of inflammatory markers in the spleen was analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Serum cytokine concentrations were detected by FACS analysis. IL-6 deficiency was highly effective in prolonging survival and ameliorating the clinical, immunological, and histological indicators of murine systemic lupus erythematosus. During the study period of 6 months, MRL-Fas(lpr) IL-6 -/- mice showed delayed onset of proteinuria and hematuria compared to IL-6-intact control mice. Survival rate was 100% in IL-6-deficient MRL-Fas(lpr) mice and 25% in the control group at 6 months of age. The absence of IL-6 resulted in significant reduction of infiltrating macrophages in the kidney (p < 0.05), a decrease in renal IgG and C3 deposition, and a reduction of CD4+ and CD8+ lymphocytes. The parenchymal adhesion molecule VCAM-1 was found to be downregulated in kidneys of MRL-Fas(lpr) IL-6 -/- compared to IL-6-intact mice. We found elevated serum levels of IL-10 and interferon-gamma in IL-6-deficient mice, while splenic mRNA showed an overall downregulation of immunoregulatory genes. IL-6 is a strong promoter of lupus nephritis and may be a promising new therapeutic target in the treatment of human lupus nephritis.

          Related collections

          Author and article information

          Comments

          Comment on this article