Serum interferon-γ and urinary monocyte chemoattractant peptide-1 are important factors in the pathogenesis of immunoglobulin A nephropathy

Background: Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN. Methods: Thirty-one patients with biopsy-proven IgAN (age, 34.48 +/- 12.10 years) and 25 healthy controls (age, 44.84 +/- 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment. Results: The levels of serum interferon-gamma (IFN gamma) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFN gamma, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFN gamma among representative Th1/Th2 cytokines. Conclusion: IFN gamma was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.