Increased production of macrophage migration inhibitory factor by T cells in patients with IgA nephropathy

K Matsumoto, K Kanmatsuse - American journal of nephrology, 2001 - karger.com
K Matsumoto, K Kanmatsuse
American journal of nephrology, 2001karger.com
Abstract Background/Aim: Several studies have demonstrated an upregulation of
macrophage migration inhibitory factor (MIF) synthesis in experimental glomerulonephritis.
To our best knowledge, no investigation of MIF production by T cells from patients with IgA
nephropathy (IgAN) has been reported so far. MIF is one of the immunoregulatory cytokines
involved in T-cell activation and delayed-type hypersensitivity. In this study, we examined
MIF production of T cells from patients with IgAN to investigate the contribution of the cells to …
Abstract
Background/Aim: Several studies have demonstrated an upregulation of macrophage migration inhibitory factor (MIF) synthesis in experimental glomerulonephritis. To our best knowledge, no investigation of MIF production by T cells from patients with IgA nephropathy (IgAN) has been reported so far. MIF is one of the immunoregulatory cytokines involved in T-cell activation and delayed-type hypersensitivity. In this study, we examined MIF production of T cells from patients with IgAN to investigate the contribution of the cells to elevated serum MIF content and to its pathologic characteristics. Methods: We measured MIF production by T cells from the peripheral blood of 20 healthy controls and 20 patients with IgAN before and approximately 10 days after the beginning of steroid therapy. The disease controls included 20 patients with minimal-change nephrotic syndrome (MCNS) before therapy. MIF concentrations in the supernatants of T-cell cultures were measured with a specific enzyme-linked immunosorbent assay (ELISA). We also investigated the relationship between MIF levels and disease activity. Results: The mean level for MIF in patients with IgAN was significantly elevated compared with that of healthy controls and also higher than that of patients with MCNS. When T cells were stimulated by concanavalin A, MIF production by T cells of patients with IgAN was more enhanced than in control subjects or patients with MCNS. We also investigated the relationship between MIF levels and pathological features in IgAN patients. Our findings reveal that MIF levels correlated with the grade of glomerular crescent formation and immunofluorescent C3 deposits in the glomeruli. Moreover, MIF overproduction was significantly related to the acute exacerbation stage of IgAN patients. Elevated MIF levels during the acute phase or exacerbations were found to be decreased during spontaneous or steroid therapy-induced remission in all IgAN patients examined. Conclusions: We provide data indicating that a T-cell population isolated by negative selection from peripheral blood mononuclear cells shows increased in vitro production of MIF in IgAN, and a reduction in that production when patients are treated with corticosteroids. In this paper, we describe the hypothetical role of MIF in the pathophysiology of IgAN.
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