Granulocyte-Colony Stimulating Factor Treatment of Lupus Autoimmune Disease in MRL-lpr/lpr Mice

摘要: G-CSF not only functions as an endogenous hemopoietic growth factor for neutrophils, but also displays pro-Th2 and antiinflammatory properties that could be of therapeutic benefit in autoimmune settings. We evaluated the effect treatment with a murine model spontaneous systemic lupus erythematosus, disease which is already administered to patients alleviate neutropenia, common complication. Chronic lupus-prone MRL- lpr/lpr mice low doses (10 μg/kg) recombinant human G-CSF, despite induction shift toward Th2 phenotype response, increased glomerular deposition Igs accelerated disease. Conversely, high-dose (200 induced substantial protection, prolonging survival by >2 mo. In animals treated these high neither Th1/Th2 profile nor serum levels TNF-α IL-10 were modified. Despite presence immune complexes their kidney glomeruli, no inflammation ensued, IL-12 soluble TNF receptors remained at pre-disease levels. This uncoupling complex damage resulted from local down-modulation FcγRIII (CD16) expression within glomeruli G-CSF. Our results demonstrate beneficial prevention nephritis may hold promise future clinical applications, provided caution taken dose adjustment.