PHYSIOLOGIC ROLE OF CYTOKINES IN LIPOPOLYSACCHARIDE

腹膜内（ip）注射脂多糖（LPS）导致 许多急性期反应，包括发烧的发展。 是 通常认为腹腔注射LPS通过引起 内源性热原（EP）释放到循环中，例如 白细胞介素-1（IL-1），肿瘤坏死因子（TNF），白细胞介素-6（IL-6）， 或者其他调解人 这些EP被认为作用于大脑， 提高体温调节设定点。 循环IL-1的作用 (and TNF和IL-6）在发展中的作用要小得多。 发热已经成为关于发病机制的中心法则的一部分， 发烧 由于一系列漂亮的间接实验 在过去的40年里支持这一假设的是， 可以理解为什么没有什么动力来评估这一点 假设更直接。 然而，很有可能目前的许多反应 归因于IL-1或其他细胞因子将变成 “药理学”而不是生理学或病理生理学。 的 拟议实验的目的是批判性地评价，在 实验室大鼠，在何种程度上LPS诱导的发热实际上涉及 这些物质在血液循环和大脑中。 的 鉴定各种假定的内源性热原，克隆 他们的特定基因，和发展的具体和敏感的 检测，现在允许测试这些假设。

Intraperitoneal (ip) injection of lipopolysaccharide (LPS) results in many acute phase responses, including the development of fever. It is generally accepted that an ip injection of LPS induces fever by causing a release into the circulation of an endogenous pyrogen (EP), such as interleukin-1 (IL-1), tumor necrosis factor (TNF), interleukin-6 (IL-6), or some other mediator. These EP's are thought to act on the brain to elevate the thermoregulatory set-point. The role of circulating IL-1 (and to a considerably lesser extent TNF and IL-6) in the development of fever has become part of the central dogma regarding the pathogenesis of fever. As a result of the beautiful sequence of indirect experiments that supported this hypothesis over the past 40 years, it is understandable why there has been little impetus to evaluate this hypothesis more directly. It is, however, quite possible that many of the responses currently attributed to IL-1 or to other cytokines will turn out to be "pharmacologic" rather than physiologic or pathophysiologic ones. The purpose of the proposed experiments is to evaluate critically, in the laboratory rat, the degree to which LPS-induced fever actually involves these substances both in the circulation and the brain. The identification of the various putative endogenous pyrogens, the cloning of their specific genes, and the development of specific and sensitive assays for them, now allow the testing of these hypotheses.