Sympathetic inhibition of IL-6, IFN-γ, and KC/CXCL1 and sympathetic stimulation of TGF-β in spleen of early arthritic mice
Sympathetic inhibition of IL-6, IFN-γ, and KC/CXCL1 and sympathetic stimulation of TGF-β in spleen of early arthritic mice
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DOI：
10.1016/j.bbi.2011.07.001
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发表时间：
2011-11-01
影响因子：
15.1
通讯作者：
Pongratz, Georg
中科院分区：
文献类型：
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作者：
Straub, Rainer H.;Rauch, Luise;Pongratz, Georg
目的：脾内交感神经纤维和免疫细胞之间的联系是已知的。在关节炎的背景下，神经免疫接触的功能意义仍然不清楚。从免疫到疾病爆发，交感神经系统（SNS）具有促炎作用，在疾病爆发后转化为抗炎作用。本研究调查了神经元释放的神经递质对IFN-γ、KC（CXCL 1）、IL-6和TGF-β在II型胶原诱导的关节炎爆发后不久的小鼠脾脏中的影响。在第32天）以产生0.35 mm厚的脾切片。将脾切片转移到灌注微室中，以电诱导交感神经递质的释放。通过这种技术，生理释放的神经递质的影响进行了研究分泌IFN-γ，KC，IL-6，和TGF-β。结果：大量的IFN-γ，KC，IL-6，和TGF-β从灌流脾释放，和电刺激显着抑制IFN-γ，KC，和IL-6的释放，但pronounedly刺激TGF-β。通过β-肾上腺素受体的肾上腺素能影响刺激IL-6，特别是TGF-β的释放。然而，儿茶酚胺抑制IL-6通过α 1-肾上腺素能途径的释放，但对TGF-β没有任何影响。共递质腺苷刺激IL-6的释放，通过A1-腺苷受体，但没有影响被确认对TGF-β。结论：在疾病爆发，电释放内源性神经递质的SNS抑制IFN-γ，KC，和IL-6，但β-肾上腺素能刺激TGF-β。这创造了一种抗炎环境，可能是SNS对关节炎的双重影响的原因。(C)2011 Elsevier Inc. All rights reserved.
Objectives: The connection between sympathetic nerve fibers and immune cells in the spleen is known. In the context of arthritis, the functional meaning of the neuroimmune contact remains unclear. From immunization until disease outbreak, the sympathetic nervous system (SNS) has a proinflammatory influence which is converted into an anti-inflammatory influence after disease outbreak. This study investigated the influence of neuronally released neurotransmitters on IFN-gamma, KC (CXCL1), IL-6, and TGF-beta in spleen of mice shortly after outbreak of collagen type II-induced arthritis.Methods: Spleens were removed when animals reached an arthritis score of 3 on a scale of 1-16 (approx. on day 32) in order to generate 0.35 mm-thick spleen slices. Spleen slices were transferred to superfusion microchambers in order to electrically induce release of sympathetic neurotransmitters. By means of this technique, the effect of physiologically released neurotransmitters was investigated on secretion of IFN-gamma, KC, IL-6, and TGF-beta.Results: High amounts of IFN-gamma, KC, IL-6, and TGF-beta were released from superfused spleen, and electrical stimulation markedly inhibited IFN-gamma, KC, and IL-6 release but pronouncedly stimulated TGF-beta. The adrenergic influence via beta-adrenoceptors stimulated release of IL-6 and, particularly, TGF-beta. However, catecholamines inhibit release of IL-6 via alpha 1-adrenergic pathways but without any effect on TGF-beta. The co-transmitter adenosine stimulated IL-6 release via A1-adenosine receptors but no influence was recognized on TGF-beta.Conclusion: At disease outbreak, electrically released endogenous neurotransmitters of the SNS inhibit IFN-gamma, KC, and IL-6 but beta-adrenergically stimulate TGF-beta. This creates an anti-inflammatory milieu that might be responsible for the observed dual influence of the SNS on arthritis. (C) 2011 Elsevier Inc. All rights reserved.