Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia to secrete the proinflammatory molecules IL-1β and CXCL8. This process is inhibited by the cytokine IL-37. Another cytokine, IL-38, has been reported to have antiinflammatory actions. In this report, we show that pretreatment of cultured adult human microglia with recombinant IL-38 (aa3-152, 1–100 ng/mL) inhibits (P < 0.0001) NT-stimulated (10 nM) secretion of IL-1β (at 1 ng/mL) and CXCL8 (at 100 ng/mL). In fact, IL-38 (aa3-152, 1 ng/mL) is more potent than IL-37 (100 ng/mL). Here, we report that pretreatment with IL-38 (100 ng/mL) of embryonic microglia (HMC3), in which secretion of IL-1β was undetectable, inhibits secretion of CXCL8 (P = 0.004). Gene expression of IL-38 and its receptor IL-36R are decreased (P = 0.001 and P = 0.04, respectively) in amygdala from patients with ASD (n = 8) compared to non-ASD controls (n = 8), obtained from the University of Maryland NeuroBioBank. IL-38 is increased (P = 0.03) in the serum of children with ASD. These findings indicate an important role for IL-38 in the inhibition of activation of human microglia, thus supporting its development as a treatment approach for ASD.

自闭症谱系障碍（ASD）的特征是社交互动和沟通障碍。ASD的发病机制尚不清楚，但涉及小胶质细胞的激活。我们已经证明，ASD儿童血清中的肽神经降压素（NT）升高，并刺激培养的成年人类小胶质细胞分泌促炎分子IL-1β和CXCL8。该过程被细胞因子IL-37抑制。据报道，另一种细胞因子IL-38具有抗炎作用。在本报告中，我们显示了用重组IL-38（aa3-152，1–100 ng / mL）对培养的成年人类小胶质细胞进行预处理可以抑制（P<0.0001）NT刺激（10 nM）的IL-1β（1 ng / mL）和CXCL8（100 ng / mL）分泌。实际上，IL-38（aa3-152，1 ng / mL）比IL-37（100 ng / mL）更有效。在这里，我们报告说，用IL-38（100 ng / mL）的胚胎小胶质细胞（HMC3）预处理（其中IL-1β的分泌无法检测到）可以抑制CXCL8的分泌（P = 0.004）。与非ASD对照（n = 8）相比，ASD患者（n = 8）的杏仁核中IL-38及其受体IL-36R的基因表达降低（分别为P = 0.001和P = 0.04）。马里兰大学NeuroBioBank。IL-38增加（P= 0.03）在ASD儿童的血清中。这些发现表明IL-38在抑制人小胶质细胞活化中起重要作用，从而支持其发展为ASD的治疗方法。