Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
Front Immunol. 2023 Oct 9;14:1165683. doi: 10.3389/fimmu.2023.1165683. eCollection 2023.
The proper functioning of the immune system depends on an appropriate balance between pro-inflammation and anti-inflammation. When the balance is disrupted and the system is excessively biased towards inflammation, immune responses cannot return within the normal range, which favors the onset of diseases of autoimmune or inflammatory nature. In this scenario, it is fundamental to find new compounds that can help restore this balance and contribute to the normal functioning of the immune system in humans. Here, we show the properties of a fungal compound with a strong safety profile in humans, AM3, as an immunomodulatory molecule to decrease excessive cytokine production in human cells. Our results present that AM3 treatment of human peripheral blood mononuclear cells and monocytes decreased their pro-inflammatory cytokine secretion following the challenge with bacterial lipopolysaccharide. Additionally, AM3 skewed the differentiation profile of human monocytes to macrophages towards a non-inflammatory phenotype without inducing tolerance, meaning these cells kept their capacity to respond to different stimuli. These effects were similar in young and elderly individuals. Thus, the fungal compound, AM3 may help reduce excessive immune activation in inflammatory conditions and keep the immune responses within a normal homeostatic range, regardless of the age of the individual.
免疫系统的正常运作依赖于促炎和抗炎之间的适当平衡。当平衡被打破,系统过度偏向炎症时,免疫反应无法恢复到正常范围,这有利于自身免疫或炎症性疾病的发生。在这种情况下,找到新的化合物来帮助恢复这种平衡并促进人类免疫系统的正常功能至关重要。在这里,我们展示了一种真菌化合物 AM3 的特性,它在人类中具有很强的安全性,作为一种免疫调节剂,可以减少人类细胞中过度的细胞因子产生。我们的结果表明,AM3 处理人外周血单核细胞和单核细胞后,可降低其在细菌脂多糖刺激下促炎细胞因子的分泌。此外,AM3 将人单核细胞向巨噬细胞的分化模式向非炎症表型倾斜,而不诱导耐受,这意味着这些细胞保持了对不同刺激的反应能力。这些作用在年轻人和老年人中相似。因此,真菌化合物 AM3 可能有助于减少炎症状态下过度的免疫激活,并使免疫反应保持在正常的动态平衡范围内,而与个体的年龄无关。