Granulocyte-colony stimulating factor treatment of lupus autoimmune disease in MRL-lpr/lpr mice

G-CSF not only functions as an endogenous hemopoietic growth factor for neu trophils, but also displays pro-Th2 and anti-inflammatory properties that c ould be of therapeutic benefit in autoimmune settings. We evaluated the eff ect of treatment with G-CSF in a murine model of spontaneous systemic lupus erythematosus, a disease in which G-CSF is already administered to patient s to alleviate neutropenia, a common complication, Chronic treatment of lup us-prone MRL-lpr/lpr mice with low doses (10 mu g/kg) of recombinant human G-CSF, despite the induction of a shift toward the Th2 phenotype of the aut oimmune response, increased glomerular deposition of Igs and accelerated lu pus disease. Conversely, high-dose (200 mu g/kg) treatment with G-CSF induc ed substantial protection, prolonging survival by >2 mo. In the animals tre ated with these high doses of G-CSF, neither the Th1/Th2 profile nor the se rum levels of TNF-alpha and IL-10 were modified. Despite the presence of im mune complexes in their kidney glomeruli, no inflammation ensued, and serum IL-12 and soluble TNF receptors remained at pre-disease levels. This uncou pling of immune complex deposition and kidney damage resulted from a local down-modulation of Fc gamma RIII (CD16) expression within the glomeruli by G-CSF. Our results demonstrate a beneficial effect of high doses of G-CSF i n the prevention of lupus nephritis that may hold promise for future clinic al applications, provided caution is taken in dose adjustment.