Binding of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids.
Binding of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids.
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DOI：
10.4049/jimmunol.153.10.4766
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发表时间：
1994-11
影响因子：
4.4
通讯作者：
William P. Arend;M. Malyak;Michael F. Smith;T. Whisenand;J. Slack;John E. Sims;J. Giri;S. Dower
中科院分区：
文献类型：
--
作者：
William P. Arend;M. Malyak;Michael F. Smith;T. Whisenand;J. Slack;John E. Sims;J. Giri;S. Dower
这些研究检测了三种IL-1配体IL-1 α、IL-1 β和IL-1受体拮抗剂（IL-1 ra）与可溶性形式的I型和II型IL-1 R（sIL-1 RI和sIL-1 RII）的结合。这种相互作用在直接结合实验中测量，其中配体结合到固定的sIL-1 R，并且在抑制实验中测量，其中溶液中的sIL-1 R抑制IL-1配体与固定的sIL-1 R的结合。此外，还研究了sIL-1 R对ELISA法检测IL-1配体的影响。最后，测定滑液样品中sIL-1 R的水平，并估计它们对这些样品中IL-1测量的影响。IL-1 β比IL-1 α或IL-1 ra更易与sIL-1 RII结合，主要是因为解离速率较慢。相反，IL-1 ra比IL-1 α或IL-1 β更容易与sIL-1 RI结合，这也是因为其解离速率较慢。sIL-1 R Ⅱ和sIL-1 R Ⅰ分别抑制IL-1 β和IL-1 ra的ELISA检测。低水平的sIL-1 RI（约1.0-2.5 ng/ml）存在于所有的滑液，无论炎症的程度，并与测量的IL-1 ra的水平呈负相关。相比之下，较高水平的sIL-1 RII（约10-20 ng/ml），发现在炎症滑液中，并没有与IL-1 ra水平。在任何滑液中均未检测到IL-1 β。这些结果表明，一些IL-1 β和IL-1 ra可能结合在体内的sIL-1 RII和sIL-1 RI，分别导致低估的体液中的细胞因子浓度时，通过ELISA测定。
These studies have examined the binding of the three IL-1 ligands, IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist (IL-1 ra), to soluble forms of types I and II IL-1Rs (sIL-1RI and sIL-1RII). This interaction was measured in direct binding experiments, in which the ligands bound to immobilized sIL-1R, and in inhibition experiments, in which sIL-1R in solution inhibited the binding of IL-1 ligands to immobilized sIL-1R. In addition, the effects of sIL-1R on the detection of IL-1 ligands by ELISA were examined. Finally, levels of sIL-1R in synovial fluid samples were determined, and their effects on measurement of IL-1 in these samples were estimated. IL-1 beta bound more avidly to sIL-1RII than IL-1 alpha or IL-1ra, primarily because of a slow dissociation rate. In contrast, IL-1 ra bound more avidly than IL-1 alpha or IL-1 beta to sIL-1RI, again because of a slow dissociation rate. sIL-1RII and sIL-1RI inhibited the detection of IL-1 beta and IL-1ra, respectively, by ELISA. Low levels of sIL-1RI (approximately 1.0-2.5 ng/ml) were present in all synovial fluids, irrespective of the degree of inflammation, and were correlated inversely with the levels of measured IL-1ra. In contrast, higher levels of sIL-1RII (approximately 10-20 ng/ml) were found in inflammatory synovial fluids and were not correlated with IL-1ra levels. IL-1 beta could not be detected in any synovial fluid. These results suggest that some IL-1 beta and IL-1ra may be bound in vivo to sIL-1RII and sIL-1RI, respectively, leading to underestimations of cytokine concentrations in body fluids when measured by ELISA.