脂多糖刺激的巨噬细胞释放的预形成热原因子。

A pre-formed Pyrogenic Factor Released by Lipopolysaccharide Stimulated Macrophages.

机构信息

Laboratory of Pharmacology Faculty of Pharmaceutical Sciences University of São Paulo Ribeirão Preto S.P. 14049-903 Brazil.

出版信息

Mediators Inflamm. 1994;3(5):365-73. doi: 10.1155/S0962935194000517.

DOI:10.1155/S0962935194000517

PMID:18475582

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2365574/

Abstract

The aim of this study was to investigate the pyrogenic activity of factor(s) released by rat peritoneal macrophages following a brief stimulation with LPS. The effect of this factor on the number of circulating leukocytes and serum Fe, Cu and Zn levels, was also evaluated. The possibility that the content of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF) in the supernatant could explain the observations was investigated. Supernatant produced over a period of 1 h by peritoneal macrophages, following a 30 min incubation with LPS at 37 degrees C, was ultrafiltered through a 10 000 MW cut-off Amicon membrane, sterilized, and concentrated 2.5, 5, 10 and 20 times. The intravenous (i.v.) injection of this supernatant induced a concentration-dependent fever in rats with a maximal response at 2 h. The pyrogenic activity was produced by macrophages elicited with thioglycollate and by resident cells. The supernatants also induced neutrophilia and reduction in Fe and Zn 6 h after the injection. Absence of activity in boiled supernatants, or supernatants from macrophages incubated at 4 degrees C with LPS, indicates that LPS was not responsible for the activity. In vitro treatment with indomethacin (Indo), dexamethasone (Dex), or cycloheximide (Chx) did not modify the release of pyrogenic activity into the supernatant or its effects on the reduction in serum metal levels. Although Chx abolished the production of mediator(s) inducing neutrophilia, and Dex reduced the induction of IL-1beta, TNF and IL-6, injection of the highest concentration of these cytokines detected in the supernatants did not induce fever. In vivo treatment with Dex, but not Indo, abolished the fever induced by the supernatant. These results suggest that macrophages contain pre-formed pyrogenic mediator(s), not related to IL-1beta, IL-6 or TNF, that acts indirectly and independently of prostaglandtn. It also seems likely that the pyrogenic activity is related to the factor responsible for the reduction of serum Fe and Zn levels, but not the neutrophilia.

摘要

本研究旨在探讨脂多糖（LPS）短暂刺激大鼠腹腔巨噬细胞后释放的因子的致热活性。还评估了该因子对循环白细胞数量以及血清铁、铜和锌水平的影响。研究了上清液中白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）的含量是否可以解释这些观察结果的可能性。将 LPS 在 37°C 孵育 30 分钟后，腹腔巨噬细胞在 1 小时内产生的上清液通过 10,000 MW 截止值 Amicon 膜超滤、消毒，并浓缩 2.5、5、10 和 20 倍。将这种上清液静脉内（i.v.）注射到大鼠体内，可引起浓度依赖性发热，最大反应发生在 2 小时。致热活性是由巯基乙醇诱导的巨噬细胞和驻留细胞产生的。注射后 6 小时，上清液还诱导中性粒细胞增多和铁、锌减少。煮沸的上清液或在 4°C 下用 LPS 孵育的巨噬细胞的上清液中无活性，表明 LPS 不是活性物质的来源。在体外用吲哚美辛（Indo）、地塞米松（Dex）或环己酰亚胺（Chx）处理不会改变致热活性的释放或其对血清金属水平降低的影响。虽然 Chx 消除了诱导中性粒细胞增多的介质的产生，而 Dex 降低了 IL-1β、TNF 和 IL-6 的诱导，但注射上清液中检测到的最高浓度的这些细胞因子并未引起发热。体内用 Dex 处理，但不用 Indo 处理，可消除上清液引起的发热。这些结果表明，巨噬细胞中含有预先形成的致热介质，与 IL-1β、IL-6 或 TNF 无关，这些介质间接且独立于前列腺素发挥作用。似乎也有可能是致热活性与导致血清铁和锌水平降低的因子有关，但与中性粒细胞增多无关。