Introduction: In arthritic mice, a sympathetic influence is proinflammatory from the time point of immunization until the onset of disease (days 0–32), but reasons are unknown. Disruption of the major anti-inflammatory pathway through G_αs-coupled receptors probably play a role. For example, noradrenaline cannot operate via anti-inflammatory β₂-adrenoceptors but through proinflammatory α_1/2-ad­renoceptors. This might happen, first, through a loss of sympathetic nerve fibers in inflamed tissue with low neurotransmitter levels (noradrenaline only binds to high-affinity α-adrenoceptors) and, second, through an alteration in G-protein receptor coupling with a predominance of α-adrenergic signaling. We hypothesized that both mechanisms play a role in the course of collagen type II-induced arthritis (CIA) in the spleen in mice. Methods: In CIA mice, nerve fiber density in the spleen was quantified by immunohistochemistry techniques. The functional impact of sympathetic nerve fibers in the spleen was studied by a micro­superfusion technique of spleen slices with a focus on the secretion of IFN-γ and IL-6 (proinflammatory) and TGF-β (anti-inflammatory). Results: During CIA, sympathetic nerve fibers get increasingly lost from day14 until day 55 after immunization. The influence of electrically released noradrenaline diminishes in the course of arthritis. At all investigated time points (days 14, 32, and 55), only proinflammatory neuronal α-adrenergic effects on cytokine secretion were demonstrated (i.e., stimulation of IFN-γ and IL-6 and inhibition of TGF-β). Conclusion: Sympathetic nerve fibers are rapidly lost in the spleen, and only proinflammatory α-adrenergic neuronal regulation of cytokine secretion takes place throughout the course of arthritis. These results support a predominance of a proinflammatory α-adrenergic sympathetic influence in arthritis.
Neuroimmunomodulation

中文翻译：

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从关节炎的第15天开始，小鼠脾脏IFN-γ，IL-6和TGF-β的促炎性α-肾上腺素能神经元调节。

简介：在关节炎小鼠中，从免疫时间点到疾病发作（0-32天）的交感神经都是促炎性的，但原因尚不清楚。通过_Gαs偶联受体破坏主要的消炎途径可能发挥了作用。例如，去甲肾上腺素不能通过抗炎性β2-肾上腺素受体起作用，而不能通过促炎性α1 _{/ 2}起作用-肾上腺素受体。这可能首先是由于低神经递质水平的发炎组织中交感神经纤维的丢失（去甲肾上腺素仅与高亲和力的α-肾上腺素受体结合），其次是通过G蛋白受体偶联改变以及占优势的α -肾上腺素信号。我们假设这两种机制均在小鼠脾脏中由II型胶原诱导的关节炎（CIA）过程中起作用。方法：采用免疫组织化学技术对CIA小鼠脾脏中神经纤维密度进行定量。通过脾脏切片的微超融合技术研究了交感神经纤维在脾脏中的功能影响，重点是IFN-γ和IL-6（促炎性）和TGF-β（消炎性）的分泌。结果：在CIA期间，从免疫后的第14天到第55天，交感神经纤维的丢失越来越多。电释放的去甲肾上腺素的影响在关节炎过程中逐渐减少。在所有调查的时间点（第14、32和55天），仅证明了促炎性神经元对细胞因子分泌的作用（即，刺激IFN-γ和IL-6和抑制TGF-β）。结论：交感神经纤维在脾脏中迅速丢失，并且在整个关节炎过程中仅发生促炎性α-肾上腺素能神经元调节细胞因子的分泌。这些结果支持了关节炎中主要的促炎性α-肾上腺素交感影响。
神经免疫调节