Abramson S, Korchak H, Ludewig R, Edelson H, Haines K, Levin R I, Herman R, Rider L, Kimmel S, Weissmann G
Proc Natl Acad Sci U S A. 1985 Nov;82(21):7227-31. doi: 10.1073/pnas.82.21.7227.
Current dogma holds that nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (e.g., indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli, such as C5-derived peptides and leukotriene B4, even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3 mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the poststimulation increase in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil activation as reflected by their capacity to inhibit movements of Ca and to enhance intracellular levels of cyclic AMP.
目前的教条认为，非甾体抗炎药（NSAIDs）通过抑制前列腺素的合成和释放起作用。然而，NSAIDs也抑制中性粒细胞的活化，中性粒细胞通过释放除前列腺素以外的产物引发炎症。我们现在报告，即使在受刺激的中性粒细胞悬液中产生的环氧化酶产物（前列腺素E和血栓烷）存在的情况下，NSAIDs（如吲哚美辛、吡罗昔康）也能抑制炎症刺激物（如C5衍生肽和白三烯B4）对中性粒细胞的活化。水杨酸钠（3 mM）极大地抑制了中性粒细胞的聚集，但对花生四烯酸诱导的血小板聚集或血栓烷的产生没有影响。水杨酸钠和其他NSAIDs也抑制钙的移动（45Ca摄取、金霉素和喹诺酮-2荧光的变化）。阿司匹林、水杨酸钠、吲哚美辛和吡罗昔康也增强了刺激后细胞内环磷酸腺苷的增加。因此，NSAIDs抑制中性粒细胞活化的早期步骤，这体现在它们抑制钙移动和提高细胞内环磷酸腺苷水平的能力上。
