Kushner I, Rzewnicki D L
Case Western Reserve University at Metrohealth Medical Center, Cleveland, OH 44109-1998.
Baillieres Clin Rheumatol. 1994 Aug;8(3):513-30. doi: 10.1016/s0950-3579(05)80113-x.
The acute phase response in a given individual represents the integrated sum of multiple, separately regulated changes. Although many of these changes commonly occur together in affected individuals, clinical experience indicates that not all of them occur in all individuals, indicating that they must be individually regulated. For example, febrile patients may have normal blood levels of CRP and vice versa, leukocytosis does not always accompany other acute phase phenomena, and many instances of discordance between levels of the various acute phase proteins are seen. Cytokines function as part of a complex regulatory network, a signalling language in which information is conveyed to cells by combinations, and perhaps sequence, of intercellular messenger molecules. The effects of combinations of cytokines are complex. To use a somewhat crude simile, individual cytokines can be thought of as words which bear informational content and which may, on occasion, communicate a complete message. More commonly, however, the actual messages received by cells probably resemble sentences, in which combinations and sequences of words convey information. Currently available data suggest that hepatocytes receive a complex mixture of humoral or paracrine signals during the acute phase response. These are integrated by multiple interacting signal transducing mechanisms to cause finely regulated changes in plasma protein synthesis. Regulation largely occurs by transcriptional control, but post-transcriptional mechanisms, including translational regulation, may also participate. Both the extracellular and intracellular mechanisms that mediate the response of the hepatocyte to inflammatory stimuli appear to be highly complex and involve multiple overlapping, concurrent and parallel pathways. Enough is known at present to conclude that IL-6 is a major participant in these plasma protein changes. Regulation of non-hepatocyte acute phase phenomena has not been delineated as thoroughly, but clearly involves a number of inflammation-associated cytokines.
特定个体的急性期反应代表了多个单独调节变化的综合总和。虽然这些变化中的许多通常在受影响的个体中同时出现，但临床经验表明并非所有变化都发生在所有个体中，这表明它们必须是单独调节的。例如，发热患者的CRP血液水平可能正常，反之亦然，白细胞增多并不总是伴随其他急性期现象，并且可以看到各种急性期蛋白水平之间存在许多不一致的情况。细胞因子作为复杂调节网络的一部分发挥作用，这是一种信号语言，其中信息通过细胞间信使分子的组合（可能还有序列）传递给细胞。细胞因子组合的作用是复杂的。用一个有点粗略的比喻来说，单个细胞因子可以被认为是带有信息内容的单词，偶尔可能传达完整的信息。然而，更常见的是，细胞实际接收到的信息可能类似于句子，其中单词的组合和序列传达信息。目前可得的数据表明，肝细胞在急性期反应期间会接收到体液或旁分泌信号的复杂混合物。这些信号通过多种相互作用的信号转导机制整合，从而导致血浆蛋白合成发生精细调节的变化。调节主要通过转录控制发生，但转录后机制，包括翻译调节，也可能参与其中。介导肝细胞对炎症刺激反应的细胞外和细胞内机制似乎都非常复杂，涉及多个重叠、并发和平行的途径。目前已知的足够多，可以得出结论，IL-6是这些血浆蛋白变化的主要参与者。非肝细胞急性期现象的调节尚未得到如此详尽的描述，但显然涉及许多与炎症相关的细胞因子。
