Straub Rainer H, Rauch Luise, Fassold Alexander, Lowin Torsten, Pongratz Georg
University Hospital Regensburg, Regensburg, Germany.
Arthritis Rheum. 2008 Nov;58(11):3450-60. doi: 10.1002/art.24030.
The sympathetic nervous system confers a proinflammatory effect during the early phase of type II collagen-induced arthritis (CIA). These effects might be mediated by up-regulation of cytokines such as interferon-gamma (IFNgamma) or chemokines such as CXCL1 (cytokine-induced neutrophil chemoattractant, or KC). This study aimed to identify the role of sympathetic neurotransmitters in splenic secretion of IFNgamma and KC shortly after the onset of CIA.
At different time points during CIA, we determined the density of sympathetic nerve fibers in the spleens of mice. Spleens were removed when the mouse joints were assessed an arthritis score of 3 (at approximately day 32). Spleen slices (0.35 mm thick) were transferred to superfusion microchambers to allow observation of the effects of physiologically released sympathetic neurotransmitters on secretion of IFNgamma and KC.
Compared with control mice, mice with CIA demonstrated a decrease in sympathetic nerve fiber density in the spleens, which reached a minimum density shortly after the start of symptomatic arthritis (day 32). T cell depletion markedly reduced splenic secretion of IFNgamma and KC. Electrical-field stimulation of the spleen slices reduced the secretion of IFNgamma, which was attenuated by an alpha1-adrenergic antagonist. In addition, splenic IFNgamma secretion was stimulated by norepinephrine, via beta-adrenergic receptors, and adenosine, via A1 adenosine receptors. Similarly, splenic KC secretion was stimulated by norepinephrine, via beta-adrenergic receptors.
The results of this study demonstrate a reduction of sympathetic nerve fibers in the spleens of arthritic animals. Nevertheless, sympathetic nerves help to increase secretion of IFNgamma and KC, which, at the early stages shortly after the onset of CIA, can contribute to the proinflammatory effect of the sympathetic nervous system.
在II型胶原诱导的关节炎（CIA）早期，交感神经系统具有促炎作用。这些作用可能由细胞因子如干扰素-γ（IFNγ）的上调或趋化因子如CXCL1（细胞因子诱导的中性粒细胞趋化因子，或KC）介导。本研究旨在确定交感神经递质在CIA发病后不久脾脏分泌IFNγ和KC中的作用。
在CIA过程中的不同时间点，我们测定了小鼠脾脏中交感神经纤维的密度。当小鼠关节的关节炎评分为3时（大约在第32天）取出脾脏。将脾脏切片（0.35毫米厚）转移至灌流微室，以观察生理释放的交感神经递质对IFNγ和KC分泌的影响。
与对照小鼠相比，CIA小鼠脾脏中交感神经纤维密度降低，在症状性关节炎开始后不久（第32天）达到最低密度。T细胞耗竭显著降低了脾脏中IFNγ和KC的分泌。对脾脏切片进行电场刺激可降低IFNγ的分泌，α1肾上腺素能拮抗剂可减弱这种作用。此外，去甲肾上腺素通过β肾上腺素能受体、腺苷通过A1腺苷受体刺激脾脏IFNγ分泌。同样，去甲肾上腺素通过β肾上腺素能受体刺激脾脏KC分泌。
本研究结果表明关节炎动物脾脏中交感神经纤维减少。然而，交感神经有助于增加IFNγ和KC的分泌，在CIA发病后不久的早期阶段，这可能有助于交感神经系统的促炎作用。
