Lee Hyun-ju, Park Hyun-Jung, Starkweather Angela, An Kyungeh, Shim Insop
Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Department of Adult Health and Nursing Systems, School of Nursing, Virginia Commonwealth University, Richmond, VA 23298-0567, USA.
Mediators Inflamm. 2016;2016:3501905. doi: 10.1155/2016/3501905. Epub 2016 Jan 19.
It has been demonstrated that immobilization (IMO) stress affects neuroimmune systems followed by alterations of physiology and behavior. Interleukin-4 (IL-4), an anti-inflammatory cytokine, is known to regulate inflammation caused by immune challenge but the effect of IMO on modulation of IL-4 expression in the brain has not been assessed yet. Here, it was demonstrated that IL-4 was produced by noradrenergic neurons in the locus coeruleus (LC) of the brain and release of IL-4 was reduced in response to IMO. It was observed that IMO groups were more anxious than nontreated groups. Acute IMO (2 h/day, once) stimulated secretion of plasma corticosterone and tyrosine hydroxylase (TH) in the LC whereas these increments were diminished in exposure to chronic stress (2 h/day, 21 consecutive days). Glucocorticoid receptor (GR), TH, and IL-4-expressing cells were localized in identical neurons of the LC, indicating that hypothalamic-pituitary-adrenal- (HPA-) axis and sympathetic-adrenal-medullary- (SAM-) axis might be involved in IL-4 secretion in the stress response. Accordingly, it was concluded that stress-induced decline of IL-4 concentration from LC neurons may be related to anxiety-like behavior and an inverse relationship exists between IL-4 secretion and HPA/SAM-axes activation.
已有研究表明，制动应激（IMO）会影响神经免疫系统，进而导致生理和行为的改变。白细胞介素-4（IL-4）是一种抗炎细胞因子，已知其可调节免疫挑战引起的炎症，但IMO对大脑中IL-4表达调节的影响尚未得到评估。在此，研究表明IL-4由大脑蓝斑（LC）中的去甲肾上腺素能神经元产生，并且IMO会导致IL-4的释放减少。研究观察到，IMO组比未处理组更焦虑。急性IMO（每天2小时，一次）刺激了血浆皮质酮的分泌以及LC中酪氨酸羟化酶（TH）的分泌，而在慢性应激（每天2小时，连续21天）情况下，这些增加量会减少。表达糖皮质激素受体（GR）、TH和IL-4的细胞定位于LC的同一神经元中，这表明下丘脑-垂体-肾上腺（HPA）轴和交感-肾上腺-髓质（SAM）轴可能参与应激反应中的IL-4分泌。因此，得出结论，应激诱导的LC神经元中IL-4浓度下降可能与焦虑样行为有关，并且IL-4分泌与HPA/SAM轴激活之间存在负相关关系。
