Effect of Mizoribine on IL-6 Release by Peripheral Blood Mononuclear Cells

Abstract

Background/Aim: A novel immunosuppressant, mizoribine (MZB), has recently been reported to be effective in the treatment of IgA nephropathy (IgAN), although its mechanism of action remains unknown. This study was conducted to investigate whether the efficacy of MZB on IgAN is exerted by suppression of interleukin-6 (IL-6) release. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 4 children with IgAN (median age 13.0 years) and 4 control children (median age 5.2 years). PBMC were cultured with medium alone or medium with lipopolysaccharide (LPS), and then incubated with LPS and MZB. Culture supernatants were assayed for lL-6. Results: IL-6 release was increased by LPS in all subjects. Although the median value was higher in IgAN patients (median increase in IL-6 release 1,298.1%) than in controls (median 489.2%), statistical significance was not reached (p > 0.05). 10 mg/ml of MZB suppressed the release of IL-6 in both IgAN patients (median decrease in IL-6 release 39.3%) and controls (median 43.2%), with statistical significance (p < 0.05 and p < 0.01, respectively). Conclusion: This study suggests that MZB could suppress IL-6 release in vitro and thus may exert its efficacy on IgAN.

Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy

“…Thus, it is possible that one of the proteinuria-lowering mechanisms of MMF is mediated through suppression of IL-6 synthesis, which is consistent with its effects in suppressing other cytokines [38]. The pathogenetic role of IL-6 in IgAN is further supported by observations that suppression of IL-6 by mizoribine, a mold extract that also selectively inhibits lymphocyte proliferation, improves glomerular lesions in childhood IgAN and in ddY mice, a rodent model of IgAN [47][48][49]. In addition, MMF has been shown in animal models of subtotal renal ablation to possess direct anti-inflammatory and antiproliferative effects that attenuate macrophage and T-cell infiltration [50], and reduce interstitial myofibroblast infiltration and collagen deposition [51].…”

Mizoribine treatment for childhood IgA nephropathy

“…We recently demonstrated that MZB significantly suppressed the IL‐6 release from peripheral blood mono­nuclear cells in vitro and suggested that this action played some role in the clinical efficacy of MZB on IgAN 26 …”

Mizoribine Promotes Molecular Chaperone HSP60/HSP10 Complex Formation

“…It has been reported that Mizoribine could suppress IL-6 release in vitro and may exert its efficacy on IgA nephropathy [ 34 ]. Mizoribine was able to inhibit the spontaneous production of IL-6 by fresh rheumatoid synovial cells (RSC) in a dose–response fashion [ 35 ].…”