IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation.
IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation.
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IL-1 受体激活会破坏全身炎症后的呼吸运动可塑性。
DOI：
10.1152/japplphysiol.01051.2017
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Huxtable,AdrianneG
中科院分区：
文献类型：
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作者：
Hocker,AustinD;Huxtable,AdrianneG
炎症会破坏呼吸运动的可塑性，然而我们才刚刚开始了解其中的炎症信号。由于白细胞介素-1 （IL-1）信号传导促进或抑制其他中枢神经系统区域的可塑性，我们验证了以下假设：1)全身炎症后IL-1受体（IL-1R）的激活对于破坏膈长期促进（pLTF）是必要的，急性间歇性缺氧（AIH）诱导的呼吸运动可塑性模型，以及2)脊髓IL-1β足以破坏pLTF。与对照组（57±25%,n= 6）相比，脂多糖（LPS, 100 μg/kg ip, 12±18%,n= 5）作用24 h后pLTF显著降低，外周IL-1R拮抗作用（63±13%,n= 5, AF-12198, 0.5 mg/kg ip, 24 h）后pLTF恢复。此外，与lps处理大鼠（11±10%,n= 5）相比，急性脊髓IL-1R拮抗剂（1 mM AF-12198, 15 μl）可恢复pLTF(53±15%,n= 4)，表明IL-1R激活是全身炎症后破坏pLTF的必要条件。然而，在健康动物中，脊髓外源性重组大鼠IL-1β (IL-1β)后pLTF持续存在（1 ng±AIH; 66±26%,n= 3,10 ng±AIH; 102±49%,n= 4,100 ng + AIH; 93±51%,n= 3,300 ng±AIH; 37±40%,n= 3；与基线相比P< 0.05）。在没有AIH的情况下，脊髓rIL-1β诱导进行性，剂量依赖性膈振幅促进（1 ng; - 3±5%,n= 3,10 ng; 8±22%,n= 3,100 ng; 31±12%，P< 0.05,n= 4,300 ng; 51±17%，P< 0.01，基线，n= 4）。综上所述，IL-1R在全身和脊柱上的激活会破坏lps诱导的全身炎症后的pLTF，但IL-1R的激活不足以消除可塑性。了解抑制呼吸可塑性的炎症信号对于开发利用呼吸可塑性促进通气控制障碍患者呼吸的治疗策略至关重要。这项研究为全身性炎症破坏呼吸运动可塑性的机制提供了新的见解。我们证明，白细胞介素-1信号，在周围和中央，破坏呼吸运动的可塑性。然而，急性的外源性白细胞介素-1信号传导并不足以破坏呼吸运动的可塑性。
Inflammation undermines respiratory motor plasticity, yet we are just beginning to understand the inflammatory signaling involved. Because interleukin-1 (IL-1) signaling promotes or inhibits plasticity in other central nervous system regions, we tested the following hypotheses:1) IL-1 receptor (IL-1R) activation after systemic inflammation is necessary to undermine phrenic long-term facilitation (pLTF), a model of respiratory motor plasticity induced by acute intermittent hypoxia (AIH), and2) spinal IL-1β is sufficient to undermine pLTF. pLTF is significantly reduced 24 h after lipopolysaccharide (LPS; 100 μg/kg ip, 12 ± 18%,n= 5) compared with control (57 ± 25%,n= 6) and restored by peripheral IL-1R antagonism (63 ± 13%,n= 5, AF-12198, 0.5 mg/kg ip, 24 h). Furthermore, acute, spinal IL-1R antagonism (1 mM AF-12198, 15 μl it) restored pLTF (53 ± 15%,n= 4) compared with LPS-treated rats (11 ± 10%;n= 5), demonstrating IL-1R activation is necessary to undermine pLTF after systemic inflammation. However, in healthy animals, pLTF persisted after spinal, exogenous recombinant rat IL-1β (rIL-1β) (1 ng ± AIH; 66 ± 26%,n= 3, 10 ng ± AIH; 102 ± 49%,n= 4, 100 ng + AIH; 93 ± 51%,n= 3, 300 ng ± AIH; 37 ± 40%,n= 3;P< 0.05 from baseline). In the absence of AIH, spinal rIL-1β induced progressive, dose-dependent phrenic amplitude facilitation (1 ng; −3 ± 5%,n= 3, 10 ng; 8 ± 22%,n= 3, 100 ng; 31 ± 12%,P< 0.05,n= 4, 300 ng; 51 ± 17%,P< 0.01 from baseline,n= 4). In sum, IL-1R activation, both systemically and spinally, undermines pLTF after LPS-induced systemic inflammation, but IL-1R activation is not sufficient to abolish plasticity. Understanding the inflammatory signaling inhibiting respiratory plasticity is crucial to developing treatment strategies utilizing respiratory plasticity to promote breathing during ventilatory control disorders.NEW & NOTEWORTHYThis study gives novel insights concerning mechanisms by which systemic inflammation undermines respiratory motor plasticity. We demonstrate that interleukin-1 signaling, both peripherally and centrally, undermines respiratory motor plasticity. However, acute, exogenous interleukin-1 signaling is not sufficient to undermine respiratory motor plasticity.