Kluger M J
Department of Physiology, University of Michigan Medical School, Ann Arbor.
Physiol Rev. 1991 Jan;71(1):93-127. doi: 10.1152/physrev.1991.71.1.93.
The biology of cytokines is one of the most rapidly growing areas of biomedical research. It is understandable why the assumption was made several years ago that EP was equivalent to IL-1 (both alpha and beta) and subsequently to IL-1 alpha, IL-1 beta, and TNF. However, as more data have been obtained, it has become clearer that many cytokines and hormones are capable of participating in the febrile response. It is also becoming apparent that EPs and ECs might influence body temperature during nonpathological states, perhaps contributing to the elevation in temperature during or after exercise, the circadian variation in temperature, and others. Medical textbooks have begun to list IL-1 as the EP. As I attempted to make clear in this review, evidence that IL-1 alpha is a circulating EP is poor. The evidence is considerably stronger that IL-1 beta is an EP, at least during LPS-induced fever in rodents. The point I have tried to emphasize is that before any cytokine or hormone can be characterized as an EP or EC (or, for that matter, as being involved in any of the acute phase responses), clearly established rules must be followed, which are patterned after the traditional criteria used by Koch to distinguish a pathogenic microorganism from a benign one. As summarized in Tables 4 and 5, there are many candidates for EPs and ECs, but much more experimental evidence is essential before we gain a clear understanding of the relationship between contact with an exogenous pyrogen, the release of EPs and ECs, and the development of fever.
细胞因子生物学是生物医学研究中发展最为迅速的领域之一。几年前有人认为内源性致热原（EP）等同于白细胞介素-1（包括α和β），随后又等同于白细胞介素-1α、白细胞介素-1β和肿瘤坏死因子（TNF），这是可以理解的。然而，随着获得的数据越来越多，越来越清楚的是，许多细胞因子和激素都能够参与发热反应。同样明显的是，EP和内源性介质（EC）可能在非病理状态下影响体温，可能导致运动期间或运动后体温升高、体温的昼夜变化等。医学教科书已开始将白细胞介素-1列为EP。正如我在本综述中试图阐明的那样，白细胞介素-1α作为循环性EP的证据不足。白细胞介素-1β作为EP的证据则要有力得多，至少在啮齿动物脂多糖诱导的发热期间是这样。我一直试图强调的一点是，在任何细胞因子或激素被确定为EP或EC（或者就此而言，被确定参与任何急性期反应）之前，必须遵循明确确立的规则，这些规则是仿照科赫用于区分病原微生物和良性微生物的传统标准制定的。如表4和表5所总结，有许多EP和EC的候选者，但在我们清楚了解与外源性致热原接触、EP和EC的释放以及发热的发展之间的关系之前，还需要更多的实验证据。
