Oral interferon-alpha treatment of mice with cryoglobulinemic glomerulonephritis

Abstract

Cryoglobulins are associated with the development of a membranoproliferative glomerulonephritis, often referred to as cryoglobulinemic glomerulonephritis, particularly in the setting of hepatitis C virus infection. Parenteral interferon-alpha (IFN-alpha) commonly is used therapeutically in humans with cryoglobulinemic glomerulonephritis. We tested the therapeutic impact of oral IFN-alpha treatment in thymic stromal lymphopoietin (TSLP) transgenic mice, a strain that develops mixed cryoglobulinemia with glomerulonephritis closely resembling the disease that occurs in humans. A total of 41 female mice were treated for 21 days with daily ingestion of either 500 IU of Universal type I IFN or placebo. The studied groups included TSLP transgenic mice treated with IFN-alpha (n = 13), TSLP transgenic mice treated with placebo (n = 13), wild-type mice treated with IFN-alpha (n = 5), and wild-type mice treated with placebo (n = 10). A total of 39 mice completed the study; two TSLP transgenic mice treated with IFN-alpha died during the study period. Placebo-treated TSLP transgenic mice showed significantly increased mean glomerular tuft areas, mean glomerular areas occupied by macrophages, and mean cell numbers per glomerulus compared with wild-type controls. All three parameters were decreased in IFN-alpha-treated TSLP transgenic mice, although the differences compared with placebo-treated mice did not reach significance. The changes in glomerular matrix deposition were the same in IFN-alpha-treated and placebo-treated mice. The oral ingestion of IFN-alpha seemed to reduce glomerular macrophage influx, but this did not result in decreased glomerular matrix deposition. The limited positive effect provides experimental support for clinical studies that indicate the beneficial effects of IFN-alpha therapy observed in humans with glomerulonephritis might be attributable to its antiviral effect rather than modulation of intrarenal pathophysiologic pathways.