Swennen Els L R, Bast Aalt, Dagnelie Pieter C
Department of Epidemiology, NUTRIM, Maastricht University, Maastricht, The Netherlands.
Eur J Immunol. 2005 Mar;35(3):852-8. doi: 10.1002/eji.200425423.
In vitro studies suggest that extracellular nucleotides and nucleosides may be important regulators of inflammatory and immune responses. Most studies with adenosine 5'-triphosphate (ATP) have been performed in cell lines, which are remote from the human situation. The purpose of the present study was to determine the effects of ATP on TNF-alpha, IL-6 and IL-10 release in stimulated whole blood. Blood samples were drawn from healthy volunteers and incubated with ATP and lipopolysaccharide (LPS) + phytohemagglutinin (PHA) for 24 h. Contrary to expectations, ATP at 100 microM and 300 microM induced a reduction in TNF-alpha secretion by 32+/-8% (mean +/- SEM) and 65+/-4%, respectively. Furthermore, these ATP concentrations induced an increase in IL-10 secretion by 48+/-5% and 62+/-7% in whole blood. The ATP analogue adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S) and adenosine 5'-diphosphate (ADP) also inhibited TNF-alpha release, but only ADP showed a stimulatory effect on IL-10. Co-treatment with adenosine deaminase did not reverse the ATP effect on TNF-alpha and IL-10. These results show, for the first time, that ATP inhibits the inflammatory response in stimulated whole blood as indicated by inhibition of TNF-alpha and stimulation of IL-10 release and that this effect is predominantly mediated by ATP and not by adenosine.
体外研究表明，细胞外核苷酸和核苷可能是炎症和免疫反应的重要调节因子。大多数关于三磷酸腺苷（ATP）的研究是在细胞系中进行的，这与人体情况相差甚远。本研究的目的是确定ATP对刺激的全血中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）释放的影响。从健康志愿者采集血样，与ATP以及脂多糖（LPS）+植物血凝素（PHA）一起孵育24小时。与预期相反，100微摩尔/升和300微摩尔/升的ATP分别使TNF-α分泌减少32±8%（平均值±标准误）和65±4%。此外，这些ATP浓度使全血中IL-10分泌分别增加48±5%和62±7%。ATP类似物5'-O-(3-硫代三磷酸)腺苷（ATP-γ-S）和二磷酸腺苷（ADP）也抑制TNF-α释放，但只有ADP对IL-10有刺激作用。与腺苷脱氨酶共同处理并不能逆转ATP对TNF-α和IL-10的作用。这些结果首次表明，ATP通过抑制TNF-α和刺激IL-10释放来抑制刺激的全血中的炎症反应，并且这种作用主要由ATP介导而非腺苷介导。
