The calcitonin and glucocorticoids combination: mechanistic insights into their class-effect synergy in experimental arthritis.
The calcitonin and glucocorticoids combination: mechanistic insights into their class-effect synergy in experimental arthritis.
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DOI：
10.1371/journal.pone.0054299
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Perretti M
中科院分区：
文献类型：
--
作者：
Al-Kashi A;Montero-Melendez T;Moradi-Bidhendi N;Gilligan JP;Mehta N;Perretti M
先前的工作报道了联合降钙素（CT）和糖皮质激素（GC）提供的抗关节炎协同作用。在这里，我们专注于依卡宁（eCT）和地塞米松（Dex）的配对，询问：i）这是否是一个类效应作用; ii）机制的见解可以揭示; iii）协同作用影响典型的GC不良反应。使用大鼠胶原诱导的关节炎模型，从疾病发作到峰值（第11天至第18天）施用eCT和Dex的不同组合。在整个过程中监测宏观疾病评分，并在第18天对血浆和组织进行生化和组织学分析。观察其对急性高脂血症和肝酶信息的影响。虽然单独使用eCT无活性，但在1 µg/kg剂量下与低剂量Dex（7.5或15 µg/kg）协同作用，产生的抗关节炎疗效相当于Dex剂量的4- 7倍。从机制上讲，抗关节炎协同作用对应于RA相关分析物的显著衰减。CXCL 5的表达，在血浆和关节，显着抑制的共同治疗。最后，eCT的联合给药没有加重GC不良反应的指标，并挽救了其中一些。我们提出了CT/GC联合抗关节炎协同作用的类效应作用的证据，其基础是对关节破坏标志物的强力抑制。此外，我们将CXCL 5确定为具有潜在诊断和预后效用的联合治疗的标志物。GC剂量的大幅降低，以及没有加重的不良反应，表明这种联合治疗在RA及其他疾病中具有显著的临床潜力。
Previous work reported the anti-arthritic synergy afforded by combining calcitonin (CT) and glucocorticoids (GC). Here we focus on the pairing of elcatonin (eCT) and dexamethasone (Dex), querying whether: i) this was a class-effect action; ii) mechanistic insights could be unveiled; iii) the synergy affected canonical GC adverse effects. Using the rat collagen-induced arthritis model, different combinations of eCT and Dex, were administered from disease onset to peak (day 11 to 18). Macroscopic disease score was monitored throughout, with biochemical and histological analyses conducted on plasma and tissues at day 18. The effect on acute hyperglycaemia and liver enzyme message were also assessed. Whilst eCT alone was inactive, it synergised at 1 µg/kg with low doses of Dex (7.5 or 15 µg/kg) to yield an anti-arthritic efficacy equivalent to a 4- to 7-fold higher Dex dose. Mechanistically, the anti-arthritic synergy corresponded to a marked attenuation in RA-relevant analytes. CXCL5 expression, in both plasma and joint, was markedly inhibited by the co-therapy. Finally, co-administration of eCT did not exacerbate metrics of GC adverse effects, and rescued some of them. We present evidence of a class-effect action for the anti-arthritic synergy of CT/GC combination, underpinned by the powerful inhibition of joint destruction markers. Furthermore, we identify CXCL5 as a marker for the combination therapy with potential diagnostic and prognostic utility. Substantial GC dose reduction, together with the absence of exacerbated adverse effects, indicated a significant clinical potential for this co-therapy in RA and beyond.
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影响因子：
6.8
作者：
Karsdal, Morten A.;Henriksen, Kim;Christiansen, Claus
通讯作者：
Christiansen, Claus
DOI：
10.1097/iae.0b013e3181ad2636
发表时间：
2009-06-01
期刊：
Retina (Philadelphia, Pa.)
影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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DOI：
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发表时间：
1990-03-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
GRIEDER, A;FELDER, M;SCHAFFNER, W
通讯作者：
SCHAFFNER, W
影响因子：
4
作者：
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通讯作者：
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