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

Abstract

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 (IFNγ) 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, IFNγ, 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 IFNγ among representative Th1/Th2 cytokines.

Conclusion: IFNγ 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.

Keywords: Chemokine CCL2; Glomerulonephritis; Interferons; T helper 1 cells; T helper 2 cells; immunoglobulin A.

Figure 1.. Level of cytokines in the serum and urine.

Comparison was performed between healthy controls and patients with IgAN. Data are presented as mean ± standard deviation. ^*p < 0.05 vs. control group. IgAN, immunoglobulin A nephropathy; IL, interleukin; INFγ, interferon-gamma; MCP-1, monocyte chemoattractant peptide-1.

Figure 2.. Level of cytokines in serum, urine, cultured PBMC, and intrarenal cytokine messenger RNA in patients grouped according to the 24-hour urinary proteinuria.

Group A: <0.5 g/day; group B: ≥0.5 and <1.0 g; group C: ≥1.0 g. Comparison was performed between the three groups. ^*p < 0.05 vs. control group. Cr, creatinie; IL, interleukin; MCP-1, monocyte chemoattractant peptide-1; NF-κB, nuclear factor kappa B; PBMC, peripheral blood mononuclear cell; TNF-α, tumor necrosis factor alpha.

Figure 3.. Monocyte chemoattractant peptide (MCP)-1 production in mesangial cells stimulated with IFNγ.

(A) Messenger RNA (mRNA) and (B) protein MCP-1 levels. Data are presented as mean ± standard deviation. ^*p < 0.05 vs. control group. IL, interleukin; INFγ, interferon-gamma; TNF-α, tumor necrosis factor alpha.