Decreased Lamina Propria Effector Cell Responsiveness to Interleukin-10 in Ileal Crohnʹs Disease

We investigated whether a lack of IL-10 production or responsiveness could be involved in Crohnʹs disease pathogenesis. Lamina propria mononuclear cells, isolated from the ilea of Crohnʹs disease patients (n = 16) and controls (n = 13), were activated with anti-CD3 mAb in the presence of CD80 transfectants or LPS ± IFN-γ. No evidence for deficient IL-10 production by either T cells or macrophages in Crohnʹs disease was found. However, the efficacy of rhIL-10 to down-regulate IFN-γ and especially TNF production in cell cultures from the involved tissues of Crohnʹs disease patients was poor, and the use of an anti-IL-10R mAb even provided evidence for proinflammatory effects of IL-10. This lack of IL-10 effect possibly results from IL-12 activity. We conclude that IL-10 exhibits poor anti- and even potential proinflammatory effects on ileal Crohnʹs disease lamina propria. These data might explain the lack of therapeutic efficacy when IL-10 is given to Crohnʹs disease patients.