RT Journal Article SR Electronic T1 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 JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 60 OP 70 DO 10.3899/jrheum.090194 VO 37 IS 1 A1 HANNES CASH A1 MANFRED RELLE A1 JULIA MENKE A1 CHRISTOPH BROCHHAUSEN A1 SIMON A. JONES A1 NICHOLAS TOPLEY A1 PETER R. GALLE A1 ANDREAS SCHWARTING YR 2010 UL http://www.jrheum.org/content/37/1/60.abstract AB Objective. To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Faslpr mice. Methods. We generated IL-6-deficient MRL-Faslpr 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. Results. 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-Faslpr 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-Faslpr 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-Faslpr IL-6 −/− compared to IL-6-intact mice. We found elevated serum levels of IL-10 and interferon-γ in IL-6-deficient mice, while splenic mRNA showed an overall downregulation of immunoregulatory genes. Conclusion. IL-6 is a strong promoter of lupus nephritis and may be a promising new therapeutic target in the treatment of human lupus nephritis.