Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis

IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokinesact as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokinesin these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokinesand C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokineassay. Cytokineconcentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokineswere significantly higher in FSNGN compared to IgAN patients. In IgAN patients ( n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokinescorrelated significantly with the presence of endocapillary proliferation, while in FSNGN patients ( n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation ( P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokinesand MIP-1 β in FSNGN. Th1, Th2 and T17 cytokineswere directly implicated in renal pathologyin IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury.