Interleukin-4 cooperates with interleukin-10 to inhibit vascular permeability factor release by peripheral blood mononuclear cells from patients with minimal-change nephrotic syndrome

Increased production of a vascular permeability factor (VPF) from peripheral blood mononuclear cells (PBMC) in patients with minimal-change nephrotic syndrome (MCNS) has been reported. Interleukin-4 (IL-4) and interleukin-10 (IL-10), both produced by T-helper type-2 cells, are cytokines with the capacity to downregulate proinflammatory responses. To gain insight into the immunoregulatory properties of these cytokines, we analyzed the effects of recombinant human IL-4 and IL-10 on VPF release in MCNS patients. In the present study we show that the regulatory cytokines IL-4 and IL-10 are potent inhibitors of the VPF activity of concanavalin A-activated MCNS PBMC. Each cytokine was found to suppress VPF release in a dose-dependent manner. Moreover, when used at suboptimal concentrations, a combination of the two cytokines resulted in enhanced suppression of VPF release. Neutralization of endogenously produced IL-4 and IL-10 by both anti-IL-4 and anti-IL-10 antibodies resulted in an increased release of VPF. These data demonstrate that IL-4 acts in concert with IL-10 to inhibit VPF release and suggest that they are effective biologic regulators of the VPF responses in vitro.